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PubMed1996

[Axonal regeneration of retinal ganglion cells].

We have developed retinal culture system of adult mammals to investigate neural regeneration from adult retinal ganglion cells (RGC). In this culture system, neurites were regenerated from RGCs of adult retinal explants. Investigation of neurotrophic effects on the neural regeneration showed that some interleukins and neurotrophins enhanced neurite regeneration from adult rat RGCs. We also found that the adult human retina had the ability of neural regeneration and that neurotrophins enhanced this ability. A novel neurotrophic factor secreted by adult rat hepatocytes also enhanced neurite regeneration not only in adult mice but also in aged RGCs. This result indicated the novel hepatocyte secreted factor is an activator which enhances neural regeneration of the aged retina. We concluded that even adult aged RGCs had the ability of axonal regeneration after injury and that neurotrophic factors might enhanced these abilities. Therefore neurotrophic factors might have practicable applications in drug treatments for intractable disease of the neural retina and optic nerve. Future progress of neuroscience is expected to rescue the retina from various diseases, and to render possible the transplantation of the retina and optic nerve.

Adult↗
PubMed1996

Prophylactic laser photocoagulation in Stickler syndrome.

The ocular manifestations in a family with Stickler syndrome and the results of laser photocoagulation as preventive treatment for retinal detachment are described. Forty-two family members with Stickler syndrome were retrospectively reviewed; 22 had ocular abnormalities, 22 had myopia and 16 had high myopia. Ten patients had developed retinal detachment and 9 of them were blind in one or both eyes because of irreparable detachment. Only 2 eyes had been operated on successfully. Ten eyes were lasered prophylactically. In eyes with extensive vitreoretinopathy laser burns were applied 360 degrees around the peripheral retina at the border between the pathological and normal retina. Eyes with isolated lesions received focal treatment around the pathological areas. Four eyes received 360 degrees laser photocoagulation and 6 eyes received focal treatment. Of the treated cases, 9 retinas remained attached for a follow-up period ranging from 1 to 15 years. One patient was lost to follow-up, and 5 years later developed retinal detachment in one eye from a new non-lasered lesion. In conclusion, in this particular family the incidence of retinal detachment was significantly higher in non-lasered eyes than in lasered eyes (p < 0.025).

Adolescent↗
PubMed1983

[Retinal detachment following extraction of an intraocular foreign body. Effects of vitrectomy].

Intra-ocular foreign bodies have an extremely poor prognosis, retinal detachment with vitreo-retinal retraction being the main factor of treatment failure. Vitrectomy appears to be an effective method for preventing this complication. 77 patients with intra-ocular foreign bodies were studied in two separate groups: 45 patients in group I did not have preventive vitrectomy and 23 developed retinal detachments; 32 patients in group II did have preventive vitrectomy within 3 weeks following foreign body extraction, and only 6 patients developed retinal detachment. Vitreous hemorrhage and cataract were present in all cases with retinal detachment. The retinal detachment rate was significatively different between group I and II. Early vitrectomy seems to be effective in preventing retinal detachment after an intra-ocular foreign body. However, others factors still have to be studied: cataract, hemorrhage, contusion.

Adolescent↗
PubMed1986

Alterations in the differentiation of chick retina caused by an intraocular injection of an alkaline phosphatase inhibitor.

Intense alkaline phosphatase (ALPase) activity has been localized in the outer plexiform layer of the developing chick retina. To elucidate the functional significance of this enzymatic activity, we have injected an ALPase inhibitor, levamisole, into embryonic eyes on either the 13th or 15th day of incubation. The retina was fixed between the 15th and 20th day of incubation and examined by electron microscopy. Levamisole injection on the 13th day caused various morphological alterations in retinal development, including the appearance of solitary photoreceptor cells in the subretinal space as well as folding of both the outer plexiform and outer nuclear layers. Pedicles of photoreceptor cells in the outer plexiform layer displayed rather smooth configurations with a reduced number of invaginations by post-synaptic neurites. The outer plexiform layer was thinned and the neuritic extensions in this layer appeared much less developed than in the control (PBS-injected) retina. Photoreceptor outer segments were seldom observed. Besides these alterations, layers of optic fibers and ganglion cells were also affected, as shown by evidence of degeneration in the ganglion cells and thinning of the nerve-fiber layer. Injection of levamisole into day 15 embryonic eyes exerted less influence on retinal development, but some photoreceptor cells were still found in the subretinal space. Some of these observations have been reported in the retinas of aged normal animals or in retinas with hereditary or induced retinal dystrophy. It is suggested that ALPase activity in the outer plexiform layer of the developing chick retina may be important for the onset of normal development of synapses in the outer plexiform layer and differentiation of the photoreceptor cells.

Alkaline Phosphatase↗
PubMed2001

Role of nitric oxide in the development of retinal projections.

Synthesis of nitric oxide (NO) occurs downstream from activation of NMDA receptors and NO acts as a retrograde messenger, influencing the refinement and stabilization of coactive afferent terminals. Cells and neuropil in the rat superior colliculus (SC) and lateral geniculate body (LGB) show intense, developmentally regulated activity for NO synthase (NOS). To study the role of NO in the development of retinogeniculate and retinotectal axon arbors, we examined primary visual projections of rats that had received daily i.p. injections of L-NoArg (an NOS inhibitor) for 4-6 weeks starting from postnatal day 0. Retinal fibers labeled by intraocular injection of the B subunit of cholera toxin were revealed immunohistochemically and the density of fibers in the superficial SC and in the dorsal LGB was measured by computerized image analysis. Single retinocollicular terminal arbors were reconstructed at the computer (Neurolucida). Treated rats showed significant alterations in ipsilateral retinotectal projections, in the mediolateral and anteroposterior axes: there was an increase in the density of fibers entering the SC, in branch length, and in numbers of boutons on retinotectal arbors in the treated group. Ipsilaterally projecting retinal axons also showed an increase in density and distribution in the dorsal nucleus of the LGB. If animals were allowed to survive for several months after stopping treatment, similar changes were also noted, but these were much less striking. Our results suggest that, in the mammalian visual system, NO released from target neurons in the SC and LGB serves as a retrograde signal which feeds back on retinal afferents, influencing their growth.

Aging↗
PubMed1985

Comparison of hydroxychloroquine and chloroquine use and the development of retinal toxicity.

We assessed the frequency of retinal toxicity in patients receiving either chloroquine or hydroxychloroquine and factors which may predict patient susceptibility to toxicity. The overall frequency of retinopathy was 6% (7 of 110 patients). Of the 31 patients receiving chloroquine alone, 6 developed toxicity (19%). In contrast, of the 66 patients receiving hydroxychloroquine, none developed retinopathy. Retinopathy was associated with greater age and with greater accumulative doses of chloroquine. Thus, hydroxychloroquine can be used safely with minimal risk of toxicity.

Adult↗
PubMed2005

Comparison of the expression patterns of five neural RNA binding proteins in the Xenopus retina.

An increasing body of evidence indicates that gene expression can be modulated by posttranscriptional mechanisms. RNA binding proteins, for instance, control gene expression at many regulatory levels including RNA splicing, transport, stability, and translation. Although numerous RNA binding proteins have been identified, very few have been studied extensively in the context of developmental processes. We focused our study on five neural RNA binding proteins: one Musashi homolog, Nrp-1, one member of the Bruno gene family, BruL-1 (also known as Etr-1), and three members of the ELAV/Hu family, ElrB, ElrC, and ElrD. As an initial step in addressing their function during Xenopus neurogenesis, we used in situ hybridization to determine their expression patterns during retinal development. We found that RNA binding proteins belonging to different families have distinct spatio-temporal expression. These combinatorial expression patterns are reminiscent of previously described cell type-specific expression patterns of transcription factors during retinal development. The distribution of RNA binding proteins within the retina suggests that these regulators of posttranscriptional events may play important roles in multiple steps of retinogenesis.

Animals↗
PubMed1999

Apoptosis during development of the human retina: relationship to foveal development and retinal synaptogenesis.

Apoptosis in the ganglion cell (GCL) and inner nuclear (INL) layers of human fetal retinae aged 14-35 weeks of gestation (WG) was investigated in relation to synaptogenesis and foveal depression formation. Terminal transferase dUTP-biotin nick end labeling (TUNEL) was used to identify apoptosis, and synapse development was demonstrated by synaptophysin immunoreactivity (-IR). The distribution of apoptotic cells and synaptophysin-IR was studied as a function of eccentricity. Between 14 and 23-24 WG in the GCL, rates of apoptosis were relatively low in central retina. A shallow fovea was detected at 23-24 WG. In the central GCL, the rate of apoptosis was 0.21% of viable cells compared with a higher incidence of 0.79-1.64% peripherally. Apoptosis in the INL was 2-8 times greater than that in the GCL. At 14-15 WG, peak death occurred at the incipient fovea; however, by 20 WG the distribution was bimodal, with peaks at more eccentric locations on either side of the incipient fovea with increasing age. Approximately 90% of INL apoptotic cells were in the middle and outer regions, suggesting that bipolar cells formed the majority of dying neurons. Synaptophysin-IR was present in cones, bipolar cells, and processes in the inner and outer plexiform layers at the incipient fovea at 14 WG and spread peripherally with increasing age. The peripheral margin of synaptophysin-IR coincided with areas of peak INL apoptosis. This pattern suggests that bipolar cell elimination is associated with the onset of synaptogenesis. Apoptosis in the GCL and INL is not a significant factor in foveal depression morphogenesis.

Apoptosis↗
PubMed1999

Stage specific glycosylation pattern for lactoseries carbohydrates in the developing chick retina.

Based on the idea of differentiation-related changes in the glycosylation pattern of neurons, the expression of two cell surface oligosaccharide epitopes, N-acetyl-lactosamine (NALA), and its sulpho-glucuronyl derivative (HNK-1), was studied, by immunohistochemistry and Western blot experiments, in the developing chick retina beginning on day 2 of incubation (E2) until day 18 post-hatching. NALA was detectable on neuroepithelial cells as soon as the primary optic vesicles formed, and this pattern continued until E3. During subsequent retinal development NALA expression became progressively restricted in concert with the appearance of postmitotic neurons as revealed by neurite outgrowth, and with the formation of synaptic contacts until it disappeared at the end of the incubation period. The pattern of NALA expression was the inverse of HNK-1 which was detected for the first time at E3 on postmitotic ganglion cells accumulating at the vitreal surface. The number of HNK-1+ cells steadily increased until around E10, when the entire neural epithelium was labelled. Synchronously to synaptogenesis, most neurons lost their HNK-1 immunoreactivity. At the time of hatching the adult-like pattern was found, characterised by subpopulations of labelled horizontal, bipolar, amacrine, and ganglion cells. Immunoblot experiments demonstrated transient NALA glycosylation of protein bands, partially identical in their apparent molecular weight to those proteins with HNK-1 glycosylation. The observed temporospatial changes in the glycosylation patterns of distinct proteins during retinal development suggest NALA as a suitable marker for neuronal proliferation, and HNK-1 for differentiation and establishment of final synaptic configuration.

Age Factors↗
PubMed2003

Scotopic electroretinogram in term infants born of mothers supplemented with docosahexaenoic acid during pregnancy.

PURPOSE: To test the hypothesis that the supplementation of the diets of pregnant women with a fish oil rich in docosahexaenoic acid (DHA) enhances retinal development in their healthy term infants, as measured during the early postnatal period by the electroretinogram (ERG). METHODS: One hundred pregnant women were randomized to receive either a fish oil (n = 50) or a placebo oleic acid dietary supplement (n = 50) from 15 weeks of pregnancy until delivery. Total fatty acids in red blood cells (RBCs) and plasma were measured in mothers at 15 and 28 weeks of pregnancy and at delivery and in their infants in umbilical cord blood. Infant retinal development was assessed within the first week of life with full-field ERGs that included a scotopic blue intensity series (n = 41) and a bright white flash (2.0 log cd-s/m(2); n = 44). RESULTS: Infants born of mothers who received supplements did not differ at birth in weight, gestational age, or any other standard variable. Infant DHA status at birth, as measured from umbilical cord blood, did not differ significantly between maternal supplementation groups. ERG implicit times, amplitudes, and parameters of the stimulus-response function did not differ significantly between infants in the maternal supplemented and placebo groups. There was, however, a relationship between infant DHA status and maturity of the retina at birth, regardless of maternal supplementation group. A measure of retinal sensitivity (log sigma) correlated significantly (P < 0.005) with DHA status (as a percentage of total fatty acid; TFA) in infant cord blood. Infants in the highest quartile for cord blood DHA had higher retinal sensitivity compared with infants in the lowest quartile. Infants in the highest quartile for plasma DHA, both as a percentage of TFA and concentration, were born at a significantly later gestational age than were infants in the lower quartiles. CONCLUSIONS: These findings demonstrate an association between the DHA status of term infants and retinal sensitivity, suggesting an essential role of this long-chain polyunsaturated fatty acid (LCPUFA) in the development and function of the retina. However, maternal DHA status was not significantly associated with infant retinal sensitivity and no direct effect of maternal supplementation was observed.

Adult↗
PubMed2002

Frequency of ciliary body or retinal breaks and retinal detachment in eyes with atopic cataract.

AIM: To determine the frequency of ciliary body or retinal breaks and retinal detachment in eyes with atopic cataract. METHODS: The records of 106 eyes (74 patients) with atopic cataract that underwent cataract extraction were reviewed. The frequency of ciliary body or retinal breaks and retinal detachment was classified by their presence preoperatively and postoperatively, and by cataract type. RESULTS: Breaks were detected preoperatively in 27 eyes (25.5%) of 17 patients in the ciliary body (20 eyes, 18.9%), near the ora serrata (five eyes, 4.7%), and in undefined locations (two eyes, 1.9%). Among these, 16 eyes (15.1%) had already developed retinal detachment. After surgery, a ciliary body break occurred in one eye (0.9%) and retinal detachment in four eyes (3.8%) of three patients. The breaks that caused postoperative retinal detachment were in the ciliary body. When classified by cataract type, the highest frequency of breaks was associated with mature cataracts (35.0%), and all eyes with breaks developed retinal detachment. CONCLUSIONS: One fourth of eyes with atopic cataract had breaks in the ciliary body or ora serrata, or retinal detachment preoperatively. The highest frequency of either breaks or retinal detachment was associated with mature cataract. The frequency of breaks or detachment that occurred postoperatively (approximately 5%) was lower than that present preoperatively.

Adolescent↗
PubMed1999

Identification of a nervous tissue-specific chondroitin sulfate proteoglycan, neurocan, in developing rat retina.

PURPOSE: To identify the expression of neurocan, a nervous tissue-specific chondroitin sulfate proteoglycan, in retina and to elucidate its changes during development. METHODS: Expressional changes of neurocan mRNAs in developing rat retinas were investigated by a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). The localization and characterization of neurocan core proteins were also investigated with the use of Western blot analysis and immunohistochemistry. RESULTS: Gene expression of neurocan was identified in retinas by RT-PCR. Semiquantitative analysis using Southern blot analysis revealed that mRNA expression for neurocan increased at increasing postnatal stages and that it reached its peak around postnatal day 7 (P7). Immunohistochemical studies demonstrated that in differentiating rat retinal (neuroblast) cells weak neurocan immunoreactivities were observed throughout the retina on embryonal days 14 (E14) and E16. During the early postnatal period, the immunoreactivities became most conspicuous in the inner and outer plexiform layers on P7 through P14. In adult retinas, only faint immunostaining was detected. Immunoblot analysis showed two positive bands of 220- and 150-kDa core glycoproteins after treatment with chondroitinase ABC. Further immunoblot analysis revealed that the expression of these two immunolabeled variants was regulated differently during retinal development. CONCLUSIONS: The temporal and spatial regulation of expression of neurocan and its proteolytic variant during retinal development suggest that it may play a role in differentiation and neural network formation.

Animals↗
PubMed2000

The SCG10-related gene family in the developing rat retina: persistent expression of SCLIP and stathmin in mature ganglion cell layer.

Neuronal growth-associated proteins (GAPs), such as GAP-43 and SCG10, are thought to play crucial roles in both axonal and dendritic outgrowth during neural development and regeneration, although the underlying mechanisms remain largely unknown. The recent finding that SCG10 is a microtubule regulator and also the identification of RB3 and SCLIP as two new SCG10-related members prompted us to investigate the roles of SCG10-related family in neural development, using the retina as a model system. We determined the temporal expression and the spatial distribution of SCG10-related mRNAs in the developing rat retina. Semiquantitative analysis by RT-PCR revealed that in prenatal retina, levels of SCG10 and stathmin mRNAs were higher than those of RB3 and SCLIP. In the postnatal retina, the level of SCLIP increased, whereas the level of RB3 remained low. In situ hybridization revealed that GAP-43 and all of the SCG10-related family mRNAs were present in the retinal ganglion cells (RGCs) at all stages of retinal development, and that stathmin mRNA was present in mitotic neuroblastic cells. Differential expression of SCG10 and other members of the family became more evident as retinal development proceeded; SCG10 and RB3 expression were relatively specific in the RGCs and amacrine cells, whereas SCLIP was also evident in bipolar and horizontal cells. Stathmin mRNA was highly expressed both in the RGCs and other interneurons. These results indicate that multiple SCG10-related proteins are expressed in single neurons including RGCs, and suggest that these nGAPs play similar but distinct roles in differentiation and functional maintenance of retinal neurons.

Animals↗
PubMed2006

Identification of genes expressed in retinal progenitor/stem cell colonies isolated from the ocular ciliary body of adult mice.

Rare pigmented cells showing retinal stem cell characteristics have been identified in the ocular ciliary body (CB) of adult mammals. In vitro, these cells were reported to clonally proliferate and generate pigmented sphere colonies (PSC) containing multipotent retinal progenitor-like cells. Because these cells may have important clinical applications and because their embryonic origin is unclear, we have analyzed their local environment and gene expression profile. We found that transcription factors Pax6, Six3, and Rx, all involved in early eye morphogenesis, were expressed in the CB of adult mice. By sequencing a PSC cDNA library, we found that PSC expressed at high levels transcripts involved in the control of redox metabolism and cellular proliferation. PSC also expressed the retinal transcription factor Six6, which expression was not detected in the CB epithelium. By in situ hybridization screen, we found that Palmdelphin (Palm), Hmga2, and a novel transcript were expressed in the central nervous system of early embryos. Palm expression delineated the pigmented epithelium of the future CB and the developing myotome. Hmga2 was expressed in the ventricular zone of the telencephalon, the developing retinal ciliary margin and lens. Several genes expressed in PSC were also expressed in the nasal anlagen. Taken together, our study reveals that PSC isolated from the ocular CB express genes involved in the control of embryonic development, retinal identity, redox metabolism, and cellular proliferation.

Animals↗
PubMed1995

Histological and ultrastructural investigation of retinal microaneurysm development in diabetic patients.

BACKGROUND: Although microaneurysms are a clinicopathological hallmark of diabetic retinopathy, there have been few ultrastructural studies of these important lesions. As a result, knowledge of the mechanisms involved in the pathogenesis of microaneurysms remains fragmentary. This study provides histological and ultrastructural evidence of various stages in microaneurysm formation within the retinal vasculature. METHODS: The eyes of three type II diabetic patients, obtained within 24 hours of death, were studied by the trypsin digest technique. Eyes from two further type II diabetics were fixed in 2.5% glutaraldehyde within 12 hours of death and processed for electron microscopy. RESULTS: In the trypsin digest preparations, small saccular and fusiform microaneurysms were observed in the peripheral retinal. In the central retina, the microaneurysms ranged in morphology from thin walled, cellular forms to dense, acellular, hyalinised forms. Ultrastructurally, four distinct groups of microaneurysm were observed. Type I showed an extensive accumulation of polymorphonuclear cells into the lumen. The endothelium remained intact, although pericytes were invariably absent. Type II microaneurysms were typified by large numbers of red blood cells (RBCs) in the lumen. Endothelial cells and pericytes were completely absent. The type III microaneurysm was also non-perfused and contained aggregates of irregularly shaped RBC profiles and RBC breakdown products. Recanalisation by new vessels into the occluded lumen was observed in one microaneurysm. Type IV microaneurysms were almost or completely sclerosed, with extensive fibrosis and lipid infiltration into the lumen and basement membrane wall. CONCLUSION: This investigation describes several distinctive stages in the formation of microaneurysms during diabetic retinopathy. With reference to the pathogenesis of retinal microaneurysms, the interaction of various cell types is discussed and the significance of vascular cell death and localised hypertensive events highlighted.

Aneurysm↗
PubMed1983

Development of retinal and cortical responses to pattern reversal in infants: a selective review.

Infant contrast sensitivity and visual acuity evaluated by recording steady-state visual evoked potentials (VEP) in response to sinusoidal gratings improve considerably during the first 6 months of life. Qualitatively similar findings are obtained in kittens 3-12 weeks old. In infants, the improvement in VEP acuity with age parallels the increase in retinal acuity estimated from electroretinographic (ERG) steady-state responses to sinusoidal gratings. Spatial frequency selective mechanisms with bandwidth substantially narrower than the overall contrast sensitivity function seem to be present in the visual system of very young infants. These findings are compared with data reported in the literature about the development of the cat and monkey visual system.

Animals↗
PubMed2004

Pathway-specific maturation, visual deprivation, and development of retinal pathway.

One of the fundamental features of the visual system is the segregation of neural circuits that process increments and decrements of luminance into ON and OFF pathways. In mature retina, the dendrites of retinal ganglion cells (RGCs) in the inner plexiform layer (IPL) of retina are separated into ON or OFF sublamina-specific stratification. At an early developmental stage, however, the dendrites of most RGCs are ramified throughout the IPL. The maturation of RGC ON/OFF dendritic stratification requires neural activities mediated by afferent inputs from bipolar and amacrine cells. The synchronized spontaneous burst activities in early postnatal developing retina regulate RGC dendritic filopodial movements and the maintenance or elimination of dendritic processes. After eye opening, visual experience further remodels and consolidates the retinal neural circuit into mature forms. Several neurotransmitter systems, including glutamatergic, acetylcholinergic, GABAergic, and glycinergic systems, might act together to modulate the RGC dendritic refinement. In addition, both the bipolar cells and cholinergic amacrine cells may provide laminar cues for the maturation of RGC dendritic stratification.

Animals↗