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PubMed1999

[Quantification of functional retinal damage in branch retinal vein thromboses].

PURPOSE: Branch retinal vein occlusion (BRVO) induces variable functional deficits depending on the grade of vascular occlusion and its localisation. Theses deficiences are not easily defined by visual acuity measurements. However, microperimetry offers topical mapping of retinal function, allowing precise documentation of the intensity and dimension of retinal functional loss in BRVO. METHODS: Retinal sensitivity was examined using a Rodenstock Scanning Laser Ophthalmoscope (SLO). A standardized grading system of stimuli ranging from 0 to 32 dB was used to document the retinal threshold in three different areas: regions presenting vascular occlusion, the collateral edematous zone and adjacent areas with intact perfusion. Absolute and relative scotomas as well as the fixation behavior were studied. RESULTS: Forty-two patients with isolated BRVO within the vascular arcades were examined with microperimetry and angiography. At initial presentation with BRVO the retinal sensitivity in the area of occlusion on average diminished to 4.1 dB. In the collateral edematous zone retinal threshold was reduced to 21.5 dB; area with intact perfusion demonstrated a threshold of 23.2 dB. Within the occluded area itself defects of significantly differing intensity were found which only partially correlated with the angiographic evidence. Intense scotomas (0 dB) were observed in 59% of the eyes examined: angiographically nonperfused areas or extended intraretinal hemorrhage were present. Relative scotomas (12.1 dB) were seen in 19.1% and minimal, non-significant defects (19.5 dB) were documented in 21.4% of the BRVO. The level of angiographically documented leakage did not correlate with the functional deficits present in these two groups. Measurements performed after 6-8 weeks revealed noticeable spontaneous recovery of retinal sensitivity, unless an additional progressive closure occurred. The average functional improvement in the area of leakage found after laser therapy was less than the results shown in spontaneous resolution of edema. CONCLUSIONS: BRVO may lead to significant reductions of central and paracentral retinal function. Angiographically observed leakage is not always directly correlated to the magnitude of retinal sensitivity loss. As spontenous remission is frequent in one group and intact retinal function can be shown in areas of angiographic leakage, therapeutic interventions, e.g., laser treatment, should be carefully considered. Scanning laser ophthalmoscopy provides additional information for precise evaluation and follow-up of the retinal damage in BRVO.

Adult↗
PubMed2002

Blockers of carbonic anhydrase can cause increase of retinal capillary diameter, decrease of extracellular and increase of intracellular pH in rat retinal organ culture.

BACKGROUND: At least in normal-pressure glaucoma a vascular genesis with hypoperfusion and regulation impairment is discussed. This may lead to malnutrition of retinal ganglion cells and apoptosis. The retinal microvasculature has a small functional reserve. In addition, the retinal microvessels lack the autonomic nerves that are normally found in other tissues. Thus, no systemic influences reach the retinal capillaries apart from circulating hormones or transmitters. Blockers of carbonic anhydrase (CA) may modulate regional blood flow by mediating changes in extra- and intracellular pH. However, it is still unclear (1) whether blockers of CA really change the pH near the retinal capillaries and (2) how changes in the local pH affect the capillary tone in situ. Therefore, we tested dorzolamide and acetazolamide in our model of the freshly enucleated rat retina. METHODS: Adult Sprague-Dawley rats (of both sexes, 250-350 g) were killed and retinae were prepared. The retinae were gently separated from the retinal pigmented epithelium and were observed in a chamber for electronic light microscopy or were fixed for immunohistochemistry. Electronic light microscopy of the retinal cells was performed with a Zeiss Axiovert microscope equipped with differential interference contrast (DIC) optics. Changes in capillary diameter were measured using an Openlab acquisition system and analyzed statistically using ANOVA. In addition to light microscopy the intracellular pH was analyzed in the whole mounts by ratio imaging of the pH using the special dye BCECF-AM (2,7 -bis-(2-carboxyethyl)-5-(and -6)-carboxyfluoresceinacetoxymethyl ester) and the extracellular pH using BCECF (2,7 -bis-(2-carboxyethyl)-5-(and -6)-carboxyfluorescein). RESULTS: Pericytes of most segments of retinal capillaries are immunoreactive for alpha-smooth muscle actin (SMA). The SMA immunostaining is strong around the nucleus; the endothelial tube is visible by virtue of the slight immunoreactivity of the surrounding pericyte processes. Acetazolamide and dorzolamide showed statistically significant vasoactive effects in retinal capillaries. Vasodilation increased by up to 105% of that in control capillaries after 5, 10 and 15 min. CA inhibitors were found to be able to induce intracellular alkalization in retinal cells. After addition of dorzolamide or acetazolamide the extracellular pH decreased from 7.4 to 7.2 concomitant with diameter changes. CONCLUSIONS: The tube-like pattern of SMA immunoreactivity demonstrates the presence of contractile elements within the pericyte processes of the rat retina. Thus, pericytes may act as a regulation element within the retinal microcirculation. Our results further suggest that CA inhibitors are able to decrease pH in the extracellular space; however, the pH within the cells increases. The increase in capillary diameter is concomitant with these pH changes. Thus, we may conclude that CA inhibitors can relax pericytes and might improve the retinal blood supply.

Acetazolamide↗
PubMed1991

Adult rat retinal glia in vitro: effects of in vivo crush-activation on glia proliferation and permissiveness for regenerating retinal ganglion cell axons.

The effects of optic nerve crush on adult rat retinal glia activation were studied in vitro. In adult rats the optic nerves were crushed and the corresponding retinae were explained 5 to 7 days later and cultured in vitro. The glial response of retinae with precrushed optic nerves was compared to the glial response of retinae without prior optic nerve crush. As a consequence of crush-axotomy more glial cells migrated out from retinal explants and covered significantly larger areas of the substratum than glia from noncrushed retinae. Migration of immunohistochemically distinguishable Vimentin-positive Müller cells and glial fibrillary acidic protein-positive astrocytes could be observed in both types of cultures. Astrocytes as well as Müller cells incorporated bromodeoxyuridine after explantation. In noncrushed retinal explants Thy 1.1-immunopositive flat cells were much more frequent and the relative proportion of glial cells was much lower than in crush-activated cultures. In a second set of experiments the ability of adult rat retinal glia to support retinal ganglion cell regeneration was examined. Normal retinal explants (without optic nerve crush) which usually do not substantially regenerate axons were cultured on retinal glia from normal and crush-activated explants. Both glia preparations supported axon growth from retinal explants after 3 days in vitro. Neuritic growth was significantly better when retinal explants from normal adult rats were cultured on crush-activated retinal glia as compared to glia derived from noncrushed retinae. It is concluded that activated adult rat retinal glia, unlike adult glia found in other brain regions, support adult rat retinal ganglion cell regeneration in vitro.

Animals↗
PubMed1989

Retinal-binding protein as a shuttle for retinal in the rhodopsin-retinochrome system of the squid visual cells.

The molluscan visual cell is characterized by having two photopigment systems, rhodopsin and retinochrome. In connection with these systems, located separately in the rhabdomal microvilli and in the nucleated cell bodies, the physiological role of retinal-binding protein (RALBP) was investigated in the squid (Todarodes pacificus) by using 3-dehydroretinal (retinal 2) as a tracer for retinal chromophore. In dark-adapted eyes, squid RALBP is combined abundantly with 11-cis-retinal. However, upon incubation with an excess of all-trans-retinal or retinol, RALBP took up great amounts of each of them, releasing its native retinoid ligands. When an all-trans-retinal-rich RALBP thus produced was incubated in the dark with metaretinochrome 2-carrying membranes, the RALBP released all-trans-retinal to the membranes to regenerate retinochrome, taking up 11-cis-retinal 2 from metaretinochrome 2. Upon further incubation of this 11-cis-retinal 2-rich RALBP with metarhodopsin-carrying membranes, the RALBP released the 11-cis-retinal 2 to the membranes to form rhodopsin 2, receiving all-trans-retinal from metarhodopsin. These findings show that squid RALBP is capable of serving as a shuttle during the recycling of retinal in the rhodopsin-retinochrome conjugate system to maintain the photoreceptive function of the visual cells.

Animals↗
PubMed2007

Characterization of early retinal progenitor microenvironment: presence of activities selective for the differentiation of retinal ganglion cells and maintenance of progenitors.

The maintenance and differentiation of retinal progenitors take place in the context of the microenvironment in which they reside at a given time during retinal histogenesis. To understand the nature of the microenvironment in the developing retina, we have examined the influence of activities present during the early stage of retinal histogenesis on enriched retinal progenitors, using the neurosphere model. Early and late retinal progenitors, enriched as neurospheres from embryonic day 14 (E14) and E18 rat retina, respectively, were cultured in embryonic day 3 (E3) chick retinal conditioned medium, simulating the microenvironment present during early retinal histogenesis. Examination of the differentiation and proliferation of retinal progenitors revealed that the early microenvironment contains at least three regulatory activities, which are partitioned in different size fractions of the conditioned medium with different heat sensitivity. First, it is characterized by activities, present in heat stable <30 kDa fraction, that promote the differentiation of retinal ganglion cells (RGCs), the early born neurons. Second, it contains activities, present in heat-sensitive >30 kDa fraction, that regulate the number of early born neurons and maintain the pool of retinal progenitors. Third, it possesses activities, present in heat-sensitive <30 kDa fraction, that prevent the premature differentiation of early retinal progenitors into the late born neurons. Thus, our observations demonstrate the regulatory influence of microenvironment on the maintenance and differentiation of retinal progenitors and establish neurospheres as a viable model system for the examination of such influences.

Animals↗
PubMed1998

Neovascular complications associated with rubeosis iridis and peripheral retinal detachment after retinal detachment surgery.

PURPOSE: To report clinical features and surgical management of neovascular complications associated with rubeosis iridis and peripheral retinal detachment after retinal detachment surgery in nondiabetic patients. METHODS: Seven consecutive eyes of seven nondiabetic patients who developed neovascular complications associated with rubeosis iridis and peripheral retinal detachment after scleral buckling and vitrectomy procedures were retrospectively reviewed. None of the eyes had clinical evidence of anterior segment ischemia or retinal vascular disease, but each eye developed rubeosis iridis and neovascular complications. RESULTS: Of the seven eyes with rubeosis iridis and peripheral retinal detachment, six developed recurrent or progressive vitreous hemorrhage, and three developed progressive neovascular glaucoma. Four eyes underwent a revision procedure to repair the peripheral retinal detachment, and anterior proliferative vitreoretinopathy was found in each of these cases. Rubeosis iridis regressed in all three eyes in which surgery resulted in complete reattachment of the retina. In one eye with persistent peripheral retinal detachment and in the three remaining eyes that did not undergo revision surgery, rubeosis iridis persisted and was associated with long-term neovascular complications. Final corrected visual acuity was 20/70 to 20/400 in three eyes with total retinal reattachment and no light perception to hand motions in four eyes with persistent peripheral retinal detachment and rubeosis iridis. CONCLUSION: Visually significant neovascular complications may occur in eyes that develop rubeosis iridis associated with peripheral retinal detachment after retinal detachment surgery in nondiabetic patients. Successful repair of the peripheral retinal detachment may induce regression of rubeosis iridis, reduce associated complications, and improve the long-term prognosis of these eyes.

Adult↗
PubMed1986

Comparison of insulin receptors from bovine retinal blood vessels and nonvascular retinal tissue.

The isolation and characterization of insulin receptors from retinal microvessels and nonvascular retinal tissue was carried out. Proteins were solubilized with Triton X-102 from retinal microvessels and nonvascular retinal tissue. The solubilized proteins were fractionated by DEAE-Sephacel ion exchange chromatography and complexed with 125I-insulin. The 125I-insulin-protein complexes were covalently cross-linked with disuccinimidyl suberate and chromatographed on a Sepharose CL-6B column. Three 125I-insulin-protein complexes with molecular weights of 560,000, 220,000 and 95,000 were obtained from both retinal microvessels and nonvascular tissue samples. The relative amount of the three complexes in retinal microvessels was about six times greater than in nonvascular retinal tissue. When aliquots of the complexes were subjected to SDS-polyacrylamide gel electrophoresis (SDS-PAGE) under non-reducing conditions, the 560,000-Da complex, which displayed the greatest specific binding of [125I]insulin, stayed at the origin; the 220,000-Da complex was dissociated into 180,000-190,000-Da and 80,000-86,000-Da components; and the 95,000-Da complex was dissociated into an 80,000-Da component. In contrast, when the cross-linked 125I-insulin-protein complexes were first reduced with dithiothreitol (DTT) and then subjected to SDS-PAGE, the 560,000-Da complex from retinal microvessels was dissociated into a 125,000-Da subunit, which is identical in size to the alpha-subunit of the insulin receptor reported in other tissues, while the 560,000-Da complex from nonvascular retinal tissue was dissociated into a 116,000-Da subunit. Upon SDS-PAGE under reducing conditions, both the 220,000-Da complex and the 95,000-Da complex from both types of retinal tissue were dissociated into 65,000-Da subunits. These results confirm that the insulin receptors of nonvascular retinal tissue exhibit structural differences from those in retinal microvessels and from insulin receptors in other tissues.

Animals↗
PubMed1997

MSL-109 adjuvant therapy for cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome: the Monoclonal Antibody Cytomegalovirus Retinitis Trial. The Studies of Ocular Complications of AIDS Research Group. AIDS Clinical Trials Group.

OBJECTIVE: To evaluate the efficacy and safety of an intravenous human monoclonal antibody to cytomegalovirus (CMV), MSL-109, as adjuvant treatment for CMV retinitis. METHODS: Two hundred nine patients with acquired immunodeficiency syndrome and active CMV retinitis were enrolled in a multicenter, phase 2/3, randomized, placebo-controlled clinical trial. Patients received adjuvant treatment with MSL-109, 60 mg intravenously every 2 weeks, or placebo. Randomization was stratified on the basis of whether patients had untreated or relapsed retinitis. Primary drug therapy for CMV retinitis was determined by the treating physician. RESULTS: The rates of retinitis progression, as evaluated in a masked fashion, were 3.04/person-year in the MSL-109-treated group and 3.05/person-year in the placebo-treated group (P=.98; Wald test); the median times to progression were 67 days in the MSL-109-treated group and 65 days in the placebo-treated group. No differences between the 2 groups were noted in the rates of increase in retinal area involved by CMV, visual field loss, or visual acuity outcomes. The mortality rate in the MSL-109-treated group was 0.68/person-year, and in the placebo-treated group, 0.31/person-year (P=.01). The mortality difference was not explained by differences in baseline variables or in concurrent antiretroviral therapy. Among patients with newly diagnosed retinitis, mortality rates were similar (MSL-109, 0.41/person-year; placebo, 0.42/person-year; P=.95), whereas among patients with relapsed retinitis the MSL-109-treated group had a greater mortality rate (MSL-109, 0.83/person-year; placebo, 0.24/person-year; P=.003). However, the mortality rate in the placebo-treated patients with relapsed CMV retinitis was lower than that in the placebo-treated patients with newly diagnosed CMV retinitis and lower than that in other trials of patients with relapsed CMV retinitis. CONCLUSIONS: Intravenous MSL-109, 60 mg every 2 weeks, appeared to be ineffective adjuvant therapy for CMV retinitis. The mortality rate was higher in the MSL-109-treated group, but the reasons for this difference remain uncertain.

AIDS-Related Opportunistic Infections↗
PubMed1993

Correlation between CD4+ counts and prevalence of cytomegalovirus retinitis and human immunodeficiency virus-related noninfectious retinal vasculopathy in patients with acquired immunodeficiency syndrome.

We prospectively studied 132 patients with acquired immunodeficiency syndrome (AIDS) to determine the cross-sectional prevalence of cytomegalovirus retinitis. All patients had serum CD4+ lymphocyte counts to determine the degree of immune dysfunction. Correlations between CD4+ counts, the presence of cytomegalovirus retinitis or human immunodeficiency virus (HIV)-related noninfectious retinal vasculopathy, and ocular symptoms were made. The study disclosed that 26 of 132 patients with AIDS (20%) had cytomegalovirus retinitis. However, subset analysis according to CD4+ count disclosed that in patients with CD4+ counts of 50 cells/mm3 or less, 26 of 87 (30%) had cytomegalovirus retinitis, whereas in patients with CD4+ counts of 50 cells/mm3 or more, none of 45 was noted to have cytomegalovirus retinitis. Similarly, 46 of 132 patients (35%) were noted to have HIV-related noninfectious retinal vasculopathy, with a trend toward increasing prevalence associated with declining CD4+ count. In patients with CD4+ counts of 50 cells/mm3 or less, 39 of 87 (45%) had HIV-related noninfectious retinal vasculopathy, whereas seven of 45 patients (16%) with CD4+ counts of 50 cells/mm3 or more were noted to have these changes. We confirmed the clinical impression that cytomegalovirus retinitis and HIV-related noninfectious retinal vasculopathy are late manifestations of AIDS, demonstrated an increased risk for patients with low CD4+ counts, and suggested a basis for coherent chemoprophylaxis and screening strategies for cytomegalovirus retinitis.

AIDS-Related Opportunistic Infections↗
PubMed1990

Combined branch retinal artery and central retinal vein obstruction.

We observed seven patients with the unusual combination of a central retinal vein obstruction in conjunction with a simultaneous branch retinal artery obstruction. The patients presented with sectoral retinal whitening, as well as diffuse peripapillary and superficial retinal hemorrhages. In five of the seven patients, the retinal hemorrhages appeared most florid in the territory of the obstructed arteriole, resulting initially in the consideration that these cases represented a combined branch retinal artery and branch retinal vein obstruction. In all cases, however, the presence of dilated, tortuous veins with diffuse retinal hemorrhages, in addition to generalized delay in arteriovenous transit on fluorescein angiography, localized the venous blockage to the central retinal vein. No intra-arterial retinal emboli were visualized. Initially, five of the seven patients suffered markedly diminished visual function; although visual acuity returned to near normal in all but two patients. In the two patients with non-resolving, markedly impaired visual acuity, neovascularization of the iris complicated the clinical course. Both of these patients were treated with panretinal photocoagulation, with resolution of the iris neovascularization. These seven patients highlight another variation of combined arterial and venous retinal vascular disease.

Adult↗
PubMed1987

[Peripheral retinal telangiectasis in retinitis pigmentosa].

The association between retinitis pigmentosa and retinal telangiectasis has been rarely reported. The case of a young woman affected with retinitis pigmentosa and telangiectasis involving bilaterally and symmetrically the inferior retinal periphery is described. Moreover, the patient showed a high degree edema of the retina produced by the permeabilization of the retinal capillaries (especially foveal capillaries) and by the passage of fluid from the choroid through the damaged retinal pigment epithelium. The telangiectasis were successfully treated with cryotherapy. The telangiectasis found in patients with retinitis pigmentosa have to be distinguished from other forms of telangiectasis, as those found in young males or those of the temporal retinal periphery of adults, in which respect they have particular characteristics. The cause of the telangiectasis and of the breakdown of the blood-retinal barrier in retinitis pigmentosa is not know. It is probable that they are produced by a toxic or inflammatory action on the vessels mediated by retinal antigens.

Adult↗
PubMed2005

PKC/MAPK signaling suppression by retinal pericyte conditioned medium prevents retinal endothelial cell proliferation.

Little is known about the regulation mechanism of endothelial cell proliferation by retinal pericytes. The purpose of this study was to elucidate the suppression mechanism of retinal capillary endothelial cell growth by soluble factors derived from retinal pericytes. Conditioned medium of retinal pericytes (rPCT1-CM) suppressed ischemia-induced retinal neovascularization. The growth and DNA synthesis of TR-iBRB2 cells, a conditionally immortalized rat retinal capillary endothelial cell line, were suppressed in a concentration-dependent manner by concentrated rPCT1-CM. The number of human cultured endothelial cells was also reduced by rPCT1-CM. These results provide the first evidence that CM from the cultivation of pericytes alone can inhibit retinal neovascularization in vivo and in vitro. Although the growth reduction of TR-iBRB2 cells was only partly reversed by treatment of rPCT1-CM with antibodies to transforming growth factor-beta1, it was completely lost by heat-treatment of rPCT1-CM, suggesting that anti-angiogenic factors are soluble proteins. The levels of expression of G1/S-phase-related proteins, such as cyclin D1, cyclin-dependent kinase (cdk)4, cdk6, and proliferating cell nuclear antigen, were reduced and a cdk inhibitor, p21(Cip1), was induced in rPCT1-CM-treated TR-iBRB2 cells. Moreover, phosphorylated p44/42 mitogen-activated protein kinase (p44/42 MAPK) in TR-iBRB2 cells was reduced by rPCT1-CM treatment and phosphorylated protein kinase C (PKC)alpha/betaII, which is upstream of p44/42 MAPK, was also suppressed. In conclusion, CM from retinal pericytes suppresses PKC-p44/42 MAPK signaling, inhibits endothelial cell growth, and prevents retinal neovascularization. Anti-angiogenic factors derived from retinal pericytes are likely to play a critical role in the regulation of retinal endothelial cell growth.

Animals↗
PubMed2002

Reliability of retinal photography in the assessment of retinal microvascular characteristics: the Atherosclerosis Risk in Communities Study.

PURPOSE: Retinal microvascular characteristics, as graded from retinal photography, have been shown to predict stroke. We evaluated the reliability of retinal photographic grading in the Atherosclerosis Risk in Communities Study. DESIGN: Cohort study. METHODS: Retinal photographs were taken of all subjects who attended the third Atherosclerosis Risk in Communities Study examination (1993 to 1995). These were graded using standardized protocols. Focal retinal characteristics were graded using a "light box" system. Generalized retinal arteriolar narrowing was quantified from computer-assisted measurements of digitized photographs. Two sub-studies were conducted to investigate the reliability of these grading methods. In the Individual Variability Study, selected subjects (n = 206) had two retinal photographs taken on one day, and a further one or two photographs taken 3 weeks later. In the Grader Variability Study, a stratified random sample of photographs had repeat retinal grading (n = 495 photographs for light box grading; n = 276 photographs for computer-assisted grading). RESULTS: Reliability of the computer-assisted quantification of generalized retinal arteriolar narrowing was high in both studies (reliability coefficients 0.64 to 0.69 for Individual Variability Study, and 0.79 to 0.83 for the Grader Variability Study). There was more variability for focal abnormalities graded using the light box system. Variability for Individual Variability Study (same individuals, repeat photographs) tended to be greater than for the Grader Variability Study (same photographs, repeat gradings). CONCLUSION: Retinal microvascular characteristics, especially computer-assisted quantification of generalized retinal arteriolar narrowing, can be ascertained reliably by standardized photographic grading methods, supporting the validity of their associations with cardiovascular disease. However, these characteristics appear to vary somewhat between eyes and over time in a single individual.

Aged↗
PubMed1998

Time-specific action of N-methyl-N-nitrosourea in the occurrence of retinal dysplasia and retinal degeneration in neonatal mice.

The morphologic response of neonatal mouse retina to the alkylating agent N-methyl-N-nitrosourea (MNU) was examined at different periods of retinal development. A dose of 60 mg/kg N-methyl-N-nitrosourea was injected intraperitoneally to neonatal C57BL mice at 0, 3, 5, 8, 11, 14, 17, and 20 days of age and to C3H mice at 0 days of age, and the retinas were examined sequentially. In the C57BL mice, MNU evoked a time-dependent occurrence of retinal dysplasia and retinal degeneration. With MNU treatment at day 0 and day 3 (the stage of retinal cell proliferation), retinal dysplasia characterized by the progressive disorganization of neuroblasts, which led to the formation of rosettes, was found in the outer neuroblastic/nuclear layer above the normal pigment epithelial cells during days 8-20, but decreased at day 50. The rosettes were surrounded by photoreceptor segments and Müller cell processes, and by photoreceptor nuclei. The MNU response was related to retinal differentiation; following MNU treatment at day 5 or 8 (the stage of retinal cell differentiation) the cells were much less sensitive (i.e. no retinal response was found). However, with MNU treatment at days 11, 14, 17, and 20 (after cellular differentiation), retinal degeneration characterized by selective photoreceptor apoptosis was seen. These results suggest that there is a critical period for the time of MNU administration in the development of mouse retinal lesions. In C3H (rd/rd) mice, MNU treatment at day 0 resulted in retinal degeneration with only slight rosette formation at the peripheral retina.

Animals↗
PubMed2005

Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures.

The retinal and cerebral microvasculatures share many morphological and physiological properties. Assessment of the cerebral microvasculature requires highly specialized and expensive techniques. The potential for using non-invasive clinical assessment of the retinal microvasculature as a marker of the state of the cerebrovasculature offers clear advantages, owing to the ease with which the retinal vasculature can be directly visualized in vivo and photographed due to its essential two-dimensional nature. The use of retinal digital image analysis is becoming increasingly common, and offers new techniques to analyse different aspects of retinal vascular topography, including retinal vascular widths, geometrical attributes at vessel bifurcations and vessel tracking. Being predominantly automated and objective, these techniques offer an exciting opportunity to study the potential to identify retinal microvascular abnormalities as markers of cerebrovascular pathology. In this review, we describe the anatomical and physiological homology between the retinal and cerebral microvasculatures. We review the evidence that retinal microvascular changes occur in cerebrovascular disease and review current retinal image analysis tools that may allow us to use different aspects of the retinal microvasculature as potential markers for the state of the cerebral microvasculature.

Aging↗
PubMed1998

Retinal projections in mice with inherited retinal degeneration: implications for circadian photoentrainment.

The availability of naturally occurring and transgenic retinal mutants has made the mouse an attractive experimental model to address questions regarding photoentrainment of circadian rhythms. However, very little is known about the retinal cells and the retinal projections to the nuclei of the murine circadian timing system. Furthermore, the effect of inherited retinal degeneration on these projections is not understood. In this report, we have used pseudorabies virus as a neuroanatomical tract tracer in mice to address a series of questions: Which retinal cells mediate circadian responses to light? What is the nature of the retinohypothalamic projection? What is the impact of the inherited retinal disorder, retinal degenerate (rd/rd), on the structures of the photoentrainment pathway? Our results show that a class ofretinal ganglion cell, morphologically similar to the type III ganglion cells of the rat, appears to project to central circadian structures of the mouse. They are few in number and sparsely distributed throughout the retina. The low number and broad distribution of these specialized retinal ganglion cells may be an adaptive mechanism to integrate environmental irradiance without compromising the spatial resolution required for vision. In addition, viral infection of conelike and rodlike photoreceptors and amacrinelike cells suggest that these cells may mediate or contribute to circadian responses to light. Inherited retinal degeneration has no obvious effect on the anatomy of the retinal cells or their projections to the circadian axis. These anatomical findings are consistent with our previous findings showing that aged rd/rd mice are capable of regulating their circadian rhythms by light with unattenuated sensitivity.

Animals↗
PubMed1990

Vitrectomy prevents retinal hypoxia in branch retinal vein occlusion.

Vitrectomy has been shown to halt diabetic retinal neovascularization, but the mechanism of this process is unknown. We propose that vitrectomy improves the oxygen supply to ischemic inner retina by way of fluid currents in the vitreous cavity. In order to test this hypothesis, we induced branch retinal vein occlusion in cats and measured preretinal oxygen tension before and after branch retinal vein occlusion in ten nonvitrectomized and five vitrectomized eyes. Branch retinal vein occlusion caused a significant decrease in preretinal oxygen tension in nonvitrectomized eyes, in which the oxygen tension fell from 20 +/- 7 to 6 +/- 5 mmHg (P = 0.001). Conversely, in vitrectomized eyes the oxygen tension was not significantly reduced after branch retinal vein occlusion. The data demonstrate that branch retinal vein occlusion causes retinal hypoxia in nonvitrectomized eyes, whereas after vitrectomy the hypoxic effect of branch retinal vein occlusion is reduced. The relief of retinal hypoxia that follows vitrectomy may be responsible for halting retinal neovascularization after vitrectomy in diabetic patients.

Animals↗
PubMed1999

Molecular cloning of retinal oxidase/aldehyde oxidase cDNAs from rabbit and mouse livers and functional expression of recombinant mouse retinal oxidase cDNA in Escherichia coli.

Retinal oxidase (EC 1.2.3.11) is a molybdenum-containing flavoenzyme with high enzymatic activity as to retinoic acid synthesis. In this study, we provide direct evidence that retinal oxidase is identical to aldehyde oxidase (EC 1.2.3.1) by cDNA cloning. Retinal oxidase and aldehyde oxidase, purified from rabbit liver cytosol using the original methods, showed completely identical HPLC patterns and amino acid sequences for three corresponding polypeptides (103 amino residues). The primary structural information obtained from the cleaved polypeptides permitted molecular cloning of the full-length cDNA of rabbit liver retinal oxidase (aldehyde oxidase). We also cloned and sequenced the full-length cDNA of mouse retinal oxidase. The cDNAs of rabbit and mouse retinal oxidase have a common sequence approximately 4.6 kb long, comprising 4-kb coding regions. The open reading frames of the cDNAs predict single polypeptides of 1334 and 1333 amino acids; the calculated minimum molecular mass of each is approximately 147,000. Northern blot analysis showed that the rabbit retinal oxidase mRNA was widely expressed in tissues. Finally, we successfully constructed a prokaryotic expression system for mouse retinal oxidase. The purified recombinant retinal oxidase from Escherichia coli showed a typical spectrum of aldehyde oxidases and a lower Km (3.8 microM) for retinal and a higher Vmax (807 nmol/min/mg protein) for retinoic acid synthesis than those of rabbit retinal oxidase (8 microM and 496 nmol/min/mg protein). This represents the first eukaryotic molybdenum-containing flavoprotein to be expressed in an active form in a prokaryotic system.

Aldehyde Oxidoreductases↗