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PubMed1973

Flux, not retinal illumination, is what cat retinal ganglion cells really care about.

1. Evidence was obtained that the impulse/quantum (I/Q) ratio of the central response mechanism of retinal ganglion cells in the cat is controlled by the steady effective retinal flux of the background.2. One experiment revealed that the I/Q ratio was decreased as the area of an adapting spot, of constant illumination, was increased. The curve relating the I/Q ratio to background flux was the same regardless of the size of the adapting spot.3. The effective central summing area of many retinal ganglion cells was determined. For the same cells, the transition level (Enroth-Cugell & Shapley, 1973) of the impulse/quantum curve was also measured. Diffuse illumination at the transition level was inversely proportional to the effective summing area, when variation in dark-adapted sensitivity between cells was taken into account.4. Therefore, retinal ganglion cells with large central summing areas are more light-adapted by any given diffuse background than cells with small centres.

Action Potentials↗

PubMed2004

Retinal circadian clocks and control of retinal physiology.

Retinas of all classes of vertebrates contain endogenous circadian clocks that control many aspects of retinal physiology, including retinal sensitivity to light, neurohormone synthesis, and cellular events such as rod disk shedding, intracellular signaling pathways, and gene expression. The vertebrate retina is an example of a "peripheral" oscillator that is particularly amenable to study because this tissue is well characterized, the relationships between the various cell types are extensively studied, and many local clock-controlled rhythms are known. Although the existence of a photoreceptor clock is well established in several species, emerging data are consistent with multiple or dual oscillators within the retina that interact to control local physiology. A prominent example is the antiphasic regulation of melaton in and dopamine in photoreceptors and inner retina, respectively. This review focuses on the similarities and differences in the molecular mechanisms of the retinal versus the SCN oscillators, as well as on the expression of core components of the circadian clockwork in retina. Finally, the interactions between the retinal clock(s) and the master clock in the SCN are examined.

Animals↗

PubMed2004

The accuracy of digital-video retinal imaging to screen for diabetic retinopathy: an analysis of two digital-video retinal imaging systems using standard stereoscopic seven-field photography and dilated clinical examination as reference standards.

PURPOSE: To evaluate the accuracy of two digital-video retinal imaging (DVRI) systems to detect diabetic retinopathy. METHODS: A prospective, masked, technology assessment was conducted for two DVRI systems at a tertiary care Veterans Affairs Medical Center. Group A (n = 151 patients) was imaged with a 640x480 resolution system and group B (n = 103 patients) with an 800x600 resolution system. Four retinal evaluations were performed on each patient: DVRI with undilated pupils using one imaging field (U-DVRI), DVRI with dilated pupils using three imaging fields (D-DVRI), dilated clinical examination, and Early Treatment Diabetic Retinopathy Study stereoscopic seven-field photography (ETDRS-P). Two analyses of accuracy were conducted, one using ETDRS-P as a "gold standard" (ETDRS-GS) and one using dilated clinical examination as a "gold standard" (C-GS). RESULTS: For group A, using the ETDRS-GS, sensitivities of U-DVRI and D-DVRI were 0.66 and 0.66; specificities of U-DVRI and D-DVRI were 0.66 and 0.86. Using the C-GS, sensitivities of U-DVRI and D-DVRI were 0.79 and 0.80; specificities of U-DVRI and D-DVRI were 0.68 and 0.85. For group B, using the ETDRS-GS, sensitivities of U-DVRI and D-DVRI were 0.76 and 0.85; specificities of U-DVRI and D-DVRI were 0.45 and 0.80. Using the C-GS, sensitivities of U-DVRI and D-DVRI were 0.81 and 0.87; specificities of U-DVRI and D-DVRI were 0.45 and 0.69. For both groups, dilation significantly improved specificities. CONCLUSIONS: The 800x600 resolution DVRI system offers an accurate method of detecting diabetic retinopathy, provided there is adequate pupillary dilation and three retinal images are taken. DVRI technology may help facilitate retinal screenings of growing diabetic populations.

Aged↗

PubMed1990

Ultrastructural and immunocytochemical changes in retinal pigment epithelium, retinal glia, and fibroblasts in vitreous culture.

Retinal pigment epithelial (RPE) cells, retinal glial, and fibroblasts, three cell types believed to play a role in the pathogenesis of epiretinal membrane formation, were maintained in vitreous culture to determine the influence of vitreous on their ultrastructure and expression of cytokeratin, glial fibrillary acidic protein (GFAP), vimentin, and glutamine synthetase (GS). Using a highly sensitive, preembedding technique for the immunolocalization of these antigens at the ultrastructural level, most RPE cells were found to lose cytokeratin and vimentin within 1 day after seeding on irradiated vitreous. The percentage of keratin-positive cells then increased with time in culture. If the vitreous was placed on RPE cells cultured in monolayer instead of placing the cells on the vitreous, keratin and vimentin were expressed these intermediate filament proteins diminished with time. Glutamine synthetase was found in RPE cells grown in monolayer with or without a vitreous overlay, but not in RPE cells grown on the surface of vitreous. Retinal glial grown on vitreous showed a time-dependent decrease in the number of cells expressing GFAP and a corresponding increase in cells expressing vimentin or GS. Some fibroblasts in vitreous culture expressed vimentin but not the other antigens evaluated. A substantial number of cells in each culture did not stain positively for cytokeratin, GFAP, vimentin, or GS. All three cell types showed phenotypic diversity at the ultrastructural level with each cell type being capable of assuming the same morphologic appearance under certain conditions. These results demonstrate the phenotypic plasticity of RPE cells, retinal glia, and fibroblasts when grown in contact with vitreous and provide further evidence that neither ultrastructure, intermediate filament protein expression, nor the presence of GS is sufficient to determine the cell type of origin of cells in epiretinal membranes.

Animals↗

PubMed1995

C-fos gene expression in rat retinal cells after focal retinal injury.

PURPOSE: To examine the expression of c-fos proto-oncogene in the rat retina after focal retinal injury. METHODS: A penetrating wound was made by pushing a 22-gauge hypodermic needle through the retina into the vitreous. The retinas were analyzed by in situ hybridization using single-stranded RNA probes for c-fos transcripts and by immunocytochemistry using anti-S100 protein antibody. RESULTS: Thirty minutes after the penetrating wound, c-fos mRNA was expressed in the inner nuclear layer (INL) and the ganglion cell layer (GCL) of the retina. Immunocytochemistry before in situ hybridization demonstrated c-fos mRNA surrounding the S-100 protein immunoreactive cytoplasm in the middle layer of the INL. CONCLUSIONS: Focal retinal injury of the rat retina induced the expression of c-fos mRNA in retinal cells. In the INL, it is suggested that the major cells that express c-fos mRNA after focal retinal injury were the Müller cells. These results suggest that c-fos may be involved in the transcription in the Müller cells after injury to the retina.

Animals↗

PubMed1994

Intranasal administration of retinal antigens suppresses retinal antigen-induced experimental autoimmune uveoretinitis.

Bovine retinal extract (RE) is a heterologous mixture of highly uveitogenic proteins including S-Antigen (S-Ag), interphotoreceptor retinol binding protein (IRBP) and rhodopsin, and is a potent inducer of experimental autoimmune uveoretinitis (EAU). Intranasal inoculation of Lewis rats with RE performed daily for 10 days prior to immunization with RE suppresses both the severity and the incidence of the clinical response and histopathological changes in EAU. Significant suppression of the disease in treated animals could be achieved with a total (cumulative) intranasal inoculum of 42 micrograms of antigen. Animals which were treated with extract exhibited a normal total antibody response to S-Ag, IRBP and retinal extract when compared with controls [phosphate-buffered saline (PBS) treated] animals. The antibody response in tolerized animals was predominantly anti-S-Ag IgG2a with suppression of anti-S-Ag IgM response. Treated animals had a significantly suppressed delayed-type hypersensitivity (DTH) response to retinal extract but normal response to purified protein derivative (PPD) compared to control animals. Adoptive transfer of splenocytes from treated animals also demonstrated some protection against RE-induced EAU. These results demonstrate that tolerance induction impairs the onset and severity of EAU by inhibiting the DTH response to heterologous mixture of retinal antigens.

Administration, Intranasal↗

PubMedDate not supplied

[Retinal as a photo-damage sensitizer of retinal-containing retina proteins].

In vision light may act as an information bearer and a dangerous injury factor. The perfection of visual reception bases on using some "details" which promote free-radical photooxidized destruction. The samples of such "details" are retinal-chromophores of all visual pigments, polyunsaturated fatty acids of photoreceptor membrane phospholipids and thiol proteins. Reliable systems protecting structure of eyes against such damage have been formed in the course of evolution process. The review of details with photosensitizing properties of retinal and some other dangerous endogenous and exogenous sensitizers of retina and retinal pigment epithelium; with mechanisms of rhodopsin and interphotoreceptor retinal binding protein photodamage; with deterioration of structure and function of photoreceptor membrane, visual cells and retina, induced by photooxidation of proteins and lipids; with aggravation role of oxygen.

Animals↗

PubMed2001

Long-term protection of retinal structure but not function using RAAV.CNTF in animal models of retinitis pigmentosa.

The present study aimed to determine whether intravitreal administration of an adeno-associated virus (AAV) carrying ciliary neurotrophic factor (CNTF) can achieve long-term morphological and physiological rescue of photoreceptors in animal models of retinitis pigmentosa, and whether injection of this virus after degeneration begins is effective in protecting the remaining photoreceptors. We injected rAAV.CNTF.GFP intravitreally in early postnatal Prph2(Rd2/Rd2) (formerly rds/rds) mice and in adult P23H and S334ter rhodopsin transgenic rats. Contralateral eyes received an intravitreal injection of rAAV.GFP or a sham injection. We evaluated the eyes at 6 months (rats) and 8.5 to 9 months (mice) postinfection and looked for histological and electoretinographic (ERG) evidence of photoreceptor rescue and CNTF-GFP expression. Intravitreal administration of rAAV resulted in efficient transduction of retinal ganglion cells in the Prph2(Rd2/Rd2) retina, and ganglion, Muller, and horizontal/amacrine cells in the mutant rat retinas. Transgene expression localized to the retinal region closest to the injection site. We observed prominent morphological protection of photoreceptors in the eyes of all animals receiving rAAV.CNTF.GFP. We found the greatest protection in regions most distant from the CNTF-GFP-expressing cells. The Prph2(Rd2/Rd2) ERGs did not exhibit interocular differences. Eyes of the rat models administered rAAV.CNTF.GFP had lower ERG amplitudes than those receiving rAAV.GFP. The discordance of functional and structural results, especially in the rat models, points to the need for a greater understanding of the mechanism of action of CNTF before human application can be considered.

Animals↗

PubMed2002

Change in retinal arterial blood flow in the contralateral eye of retinal vein occlusion during glucose tolerance test.

PURPOSE: To investigate the changes in retinal blood flow (RBF) during a 75-g oral glucose tolerance test in the contralateral eye of patients with retinal branch vein occlusion (BRVO). METHODS: Seventeen patients with BRVO were included. None had a known history of diabetes mellitus. The blood velocity and vessel diameter of the upper temporal retinal artery in the contralateral eye were measured using laser Doppler velocimetry with an eye-tracking system before and 1, 2, and 3 h after oral intake of 75 g glucose. Blood sugar, systemic blood pressure, and intraocular pressure were monitored. Eleven healthy volunteers were examined similarly as control. RESULTS: Nine patients (53%) with BRVO had an abnormal pattern on the glucose tolerance test. RBF significantly increased at 1, 2, and 3 h in eight patients with normal glucose tolerance. The changes in RBF primarily resulted from changes in vessel diameter; the blood velocity did not change significantly. The nine patients with impaired glucose tolerance or diabetes mellitus had a RBF pattern that was significantly lower at 2 and 3 h than those with normal oral glucose tolerance. In the control group, all 11 volunteers showed the same increases in RBF at 2 and 3 h as the BRVO patients with a normal glucose pattern. CONCLUSION: A relatively high number of patients with BRVO had an abnormal pattern on glucose tolerance testing. Glucose intake increased RBF in BRVO patients without diabetes and in healthy volunteers. The RBF response may differ between subjects with diabetes and those without diabetes.

Aged↗

PubMedDate not supplied

Retinal blood flow in the macular area before and after scleral buckling procedures for rhegmatogenous retinal detachment without macular involvement.

PURPOSE: To investigate retinal microcirculation changes in patients with rhegmatogenous retinal detachment (RRD). METHODS: The tissue blood flow in the macular area was measured in 28 patients with RRD without macular involvement by scanning laser Doppler flowmetry before and after scleral buckling procedures. The mean blood flow (MBF) was calculated by the automatic full-field analysis program. The MBF ratios of the affected eye to the fellow eye (a/f ratio) in patients were compared with those of the right eye to the left eye (R/L ratio) in the control subjects. RESULTS: The mean preoperative a/f ratio in the patients (0.81 +/- 0.11) was lower than the mean R/L ratio in the control subjects (1.02 +/- 0.11, P < 0.0001) and correlated with the extent of RRD (P < 0.05). The mean a/f ratio tended to decrease 2 weeks after surgery (0.72 +/- 0.09) and recovered to an almost normal level after 1 month (0.96 +/- 0.09). The blood-flow change was not influenced by the type of buckling. CONCLUSIONS: The retinal microcirculation in the macular area was disturbed in RRD patients without macular involvement. It correlated with the extent of the RRD, and subsided 1 month after successful scleral buckling procedures.

Adolescent↗

PubMed2006

Retinal blood flow and macular edema after radial optic neurotomy for central retinal vein occlusion.

PURPOSE: To determine the effect of radial optic neurotomy (RON) on retinal blood flow (RBF) and macular edema in eyes with a central retinal vein occlusion. DESIGN: Prospective interventional study. METHODS: Seven eyes of seven patients with central retinal vein occlusion underwent RON and vitrectomy and were followed for at least 6 months. The RBF was calculated from dye dilution curves of video fluorescein angiograms. The foveal thickness was determined by optical coherence tomography. RESULTS: At 1 week after surgery, the RBF was significantly reduced from 28.5 +/- 5.4 to 21.1 +/- 6.6 pixel(2)/s (P < .01). At 6 months after surgery, the RBF (26.0 +/- 7.7 pixel(2)/s) was not significantly different from the preoperative RBF, although chorioretinal anastomoses were found in all seven eyes. The foveal thickness was significantly decreased from 711 +/- 271 to 488 +/- 182 mum (P = .03). The postoperative visual acuity was better than the preoperative visual acuity by two or more lines in three out of seven eyes, and was worse in two eyes. CONCLUSIONS: Neither RON nor chorioretinal anastomoses improved the RBF but macular edema was improved. These findings suggest that removal of the vitreous could reduce macular edema as in diabetic macular edema. However, we cannot exclude the possibility that the changes represent the natural course of this disease.

Adult↗

PubMed1992

Repair of retinitis-related retinal detachments with silicone oil in patients with acquired immunodeficiency syndrome.

To provide prompt visual rehabilitation and to reduce the need for repeated operations, we performed vitrectomy with silicone oil tamponade in 16 consecutive eyes with retinal detachments related to cytomegalovirus retinitis and acute retinal necrosis in 13 patients with acquired immunodeficiency syndrome. In all 16 eyes (100%), retinas were reattached with one operation. Preservation of ambulatory vision was achieved in six of eight eyes (75%; mean follow-up, 14.6 weeks). No patient with hand motion visual acuity or worse preoperatively recovered ambulatory vision. Visual acuity recovery was limited by optic nerve disease in five eyes (31%). Silicone oil-related side effects did not adversely affect visual outcome in any eye. Six patients (46%) have since died (mean, 4.4 months postoperatively). These data indicated that successful surgical repair of these detachments can be consistently achieved with this approach. The prognosis for ambulatory vision is strongly related to preoperative visual acuity.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Branch retinal vein occlusion in the right eye and retinal hemorrhage in the left in a patient with classical Tsutsugamushi disease.

PURPOSE: To report branch retinal vein occlusion and retinal hemorrhages associated with tsutsugamushi disease. METHODS: Case report of a 60-year-old woman who complained of fever, chills, headache, lymphadenopathy, and blurred vision in the right eye following an insect bite to the lower right forehead. RESULTS: Serological findings showed elevated titers for the strains of Rickettsia tsutsugamushi. Ophthalmologic examination disclosed bilateral conjunctival injection, flame-shaped hemorrhage in her right fundus, and scattered hemorrhage in her left fundus. Fluorescein angiography demonstrated dye leakage and dilation of capillaries. CONCLUSIONS: Branch retinal vein occlusion associated with classical tsutsugamushi disease, as demonstrated in our patient, may be rare.

Antibodies, Bacterial↗

PubMed2002

Retinal oxygen saturation levels in patients with central retinal vein occlusion.

PURPOSE: To validate the efficacy of Fourier transform-based spectral retinal imaging (SRI) in quantifying retinal ischemia. DESIGN: Prospective, observational case series. PATIENTS AND METHODS: Eleven eyes of 10 patients with central retinal vein occlusion (CRVO) and 4 fellow unaffected eyes of selected patients were examined by both fluorescein angiography and SRI. The fluorescein angiograms were correlated with oxygen saturation maps that were calculated from the SRI. RESULTS: Oxygen saturation levels in the fundus were shown as color grading in 35 degrees fundus images processed by SRI. This grading correlated well with the severity of CRVO, as estimated by fluorescein angiography. CONCLUSIONS: The severity of circulatory disturbances in CRVO may be graded by applying SRI.

Blood Flow Velocity↗

PubMed2003

Scanning laser polarimetry of the retinal nerve fiber layer in central retinal artery occlusion.

PURPOSE: To report the results of scanning laser polarimetry (NFA/GDx; Laser Diagnostic Technologies, San Diego, CA). DESIGN: Prospective, consecutive observational case series. PARTICIPANTS: Ten consecutive patients with central retinal artery occlusion (CRAO). METHODS: Neuro-ophthalmic examination and scanning laser polarimetry of the retinal nerve fiber layer (RNFL) of 10 patients with CRAO. MAIN OUTCOME MEASURES: Duration of visual loss, visual acuity, funduscopy, and scanning laser polarimetry of the RNFL in 10 eyes of 10 patients with CRAO. RESULTS: The duration of visual loss before examination and scanning laser polarimetry ranged from 1 to 7 days. Visual acuity was counting fingers at 1 foot or worse in all 10 eyes with CRAO, and funduscopy revealed pallid retinal edema accompanied by a cherry red spot in all affected eyes. Funduscopy of the fellow eyes in all but one patient, who had anterior ischemic optic neuropathy and was subsequently diagnosed with giant cell arteritis, revealed no acute changes. Scanning laser polarimetry of all eyes with CRAO revealed diffuse attenuation of the retardation of the RNFL. Scanning laser polarimetry of the fellow eye revealed a normal bimodal distribution in the eight patients in whom it could be measured. In one patient who was examined 1 day after the onset of visual loss, repeat nerve fiber analysis 6 weeks later revealed further depression of the RNFL compared with the initial scan. Repeat analysis of the RNFL in four other patients showed persistence of the diffuse depression noted during their initial examinations. CONCLUSIONS: Scanning laser polarimetry in CRAO reveals diffuse depression of the retardation of the RNFL, which occurs acutely after the onset of visual loss. To our knowledge these patients represent the first reports of scanning laser polarimetry of the RNFL in acute CRAO.

Adult↗

PubMed1988

Photocoagulation to prevent retinal detachment in acute retinal necrosis.

Retinal detachment (RD) occurs in more than 50% of eyes with acute retinal necrosis (ARN) and is the leading cause of visual loss in this syndrome. In order to decrease the incidence of RD in ARN, the authors treated 12 eyes of 10 patients with prophylactic laser photocoagulation. Retinal detachment occurred in two eyes (17%). Over the same time period, seven eyes with ARN did not receive prophylactic laser treatment, most often because of dense vitreous debris, with a 67% rate of RD. Prophylactic photocoagulation treatment should be considered in the management of patients with ARN.

Acute Disease↗

PubMed1998

Retinal blood flow in nonischemic central retinal vein occlusion.

OBJECTIVE: The authors studied the changes in retinal blood flow (RBF) and oxygen reactivity in a major temporal vein in patients with central retinal vein occlusion (CRVO). PARTICIPANTS: Eleven patients with nonischemic CRVO approximately 7 weeks from onset of disease. INTERVENTION: Laser Doppler velocimetric measurement of RBF and vessel reactivity to inhaling 60% oxygen. Measurements were performed at baseline and 3 months. RESULTS: Flow velocity in the affected eye had increased significantly by 3 months, from 1.6 +/- 0.4 cm/second to 2.0 +/- 0.4 cm/second (P = 0.02). Retinal blood flow, however, remained unchanged (13.7 +/- 5.8 microl/minute versus 15.0 +/- 6.5 microl/minute). The two comparable RBF values, despite differing velocity values, suggest that the relatively normal baseline value was achieved through higher intravascular pressure at baseline (Bernoulli's principle). This is supported by the fact that oxygen reactivity had improved from 2.1% +/- 3.6% at baseline to 3.8% +/- 3.1% (P = 0.001) at 3 months, which suggests an improved ability to respond to hyperoxia from reduced intravascular pressure. CONCLUSION: Intravascular pressure in CRVO appears to continue to decrease during the first 5 months after the onset of CRVO, indicating continuing reduction in the degree of outflow obstruction during this time.

Blood Flow Velocity↗

PubMed1993

Mutations in the human retinal degeneration slow (RDS) gene can cause either retinitis pigmentosa or macular dystrophy.

Mutations in the RDS gene, which encodes the photoreceptor glycoprotein peripherin, have been sought in families with autosomal dominant retinal dystrophies. A cysteine deletion at codon 118/119 is associated with retinitis pigmentosa in one. Three families with similar macular dystrophy have mutations at codon 172, arginine being substituted by tryptophan in two and by glutamine in one. A stop sequence at codon 258 exists in a family with adult vitelliform macular dystrophy. These findings demonstrate that both retinitis pigmentosa and macular dystrophies are caused by mutations in RDS and that the functional significance of certain amino-acids in peripherin-RDS may be different in cones and rods.

Adult↗