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PubMed2006

Role of apoptosis signal-regulating kinase 1 in stress-induced neural cell apoptosis in vivo.

Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that plays an important role in oxidative stress-induced apoptosis. In the present study, we used ASK1 knockout (KO) mice to examine the possibility that ASK1 is involved in the neural cell apoptosis that occurs during retinal development and ischemic injury. ASK1 was expressed in retinal neurons, including retinal ganglion cells (RGCs), but retinal structure and extent of cell death during development were normal in ASK1 KO mice. On the other hand, the strain was less susceptible to ischemic injury, and the number of surviving retinal neurons was significantly increased compared with that in wild-type mice. Interestingly, ischemia-induced phosphorylation of p38 mitogen-activated protein kinase (p38), which mediates RGC apoptosis, was almost completely suppressed in ASK1 KO mice. In such retinas, the numbers of cleaved caspase-3- and TUNEL-positive neurons were apparently decreased compared with those in wild-type mice. Furthermore, cultured RGCs from ASK1 KO mice were resistant to H(2)O(2)-induced apoptosis. Our findings suggest that ASK1 is involved in the neural cell apoptosis after various kinds of oxidative stress. Thus, inhibition of the ASK1-p38 pathway could be useful for the treatment of neurodegenerative diseases including glaucoma.

Animals↗
PubMed1994

Photoreceptor outer segment development in Xenopus laevis: influence of the pigment epithelium.

Opsin gene expression, synthesis, and photoreceptor outer segment morphology were evaluated during retinal development in Xenopus laevis. Retinal rudiments were harvested during in vivo development from embryonic stages 31 through 46 or were allowed to develop in vitro after removal from stage 33/34 embryos for 1, 2, or 3 days either with or without an investing pigment epithelium. Opsin mRNA was detected at stage 33/34 and the transcript level increased until stage 40 and remained at this level through stage 46. Opsin was first detected at stage 37/38 and progressively increased through stage 46. Rudimentary photoreceptor outer segment membranes occasionally appeared as early as stage 33/34 and they gradually increased in length, forming well-defined stacks of collapsed membranous saccules (discs) during in vivo development. The maturation of eye rudiments in culture was followed to determine how closely in vivo and in vitro development compare and to examine the ability of photoreceptors to differentiate when maintained in the absence of an overlying pigment epithelium (PE) layer. With the PE present, opsin mRNA as well as opsin content steadily increased over the entire culture period. After 1 day of culture, short cilia with minimal amounts of outer segment membranous material were present. By Day 3, the degree of outer segment differentiation corresponded morphologically to approximately stage 43 of in vivo development. When cultured in the absence of an investing PE, the opsin mRNA level increased minimally during the 3 days in culture. Opsin content increased, yet the relative amount was approximately 50% less than that present in retinas developing in the presence of the PE. Membranous material was elaborated; however, the outer segments appeared to be highly disorganized and formed whorl-like structures rather than the normal stacked disc morphology. These results suggest that the PE may be involved in regulating opsin at the transcriptional and/or translational levels and also participates in the organization of rod outer segment membranes.

Animals↗
PubMed2003

Expression of cytokine signal transduction components in the postnatal mouse retina.

PURPOSE: Members of the ciliary neurotrophic factor (CNTF) family of cytokines have been shown to influence neuronal differentiation during retinal development and enhance cell survival in various retinal degeneration models. However, the cellular mechanism of CNTF signaling and the target cell types for CNTF in the developing retina remain unidentified. The purpose of this study is to characterize expression patterns of proteins involved in cytokine signal transduction in the mouse retina, thus to assess the potential responsiveness of different retinal cell types to CNTF-like cytokine signals. METHODS: The expression profiles of various cytokine signal transduction components, including receptor subunits CNTF receptor alpha (CNTFRa) and gp130, intracellular protein kinases, Jak2 and Tyk2, as well as latent transcription factors, STAT1 and STAT3, were determined by immunohistochemical staining of mouse retinal sections derived from different postnatal stages. In addition, the distribution of ERK was studied by immunofluorescent staining. RESULTS: In the neonatal retina, intense staining signals for gp130, CNTFRalpha, Jak2, Tyk2, STAT1, and STAT3 were present in the differentiated ganglion cell layer and the developing inner plexiform layer of the mouse retina. Detectable staining signals were also observed in the ventricular zone of the early postnatal mouse retina. From P5 to P10, cytokine signaling molecules also accumulated in the developing outer plexiform layer. In the adult retina, cytokine signaling components examined were localized to the ganglion cell layer, the inner nuclear layer, and the two plexiform layers. In addition, regions corresponding to the inner and/or outer segments of the photoreceptor cells showed positive staining for cytokine signaling components. In contrast, the ERK2 protein kinase was found throughout the neonatal retina. In the mature retina, ERK2 was concentrated in the ganglion cells and the inner plexiform layer, while a lesser expression of ERK2 was detected in the inner nuclear layer, the outer plexiform layers, and the outer nuclear layer. CONCLUSIONS: In the neonatal mouse retina, signaling components of the Jak-STAT pathway and ERK2 are differentially expressed. All cytokine signaling components included in this study are expressed in the differentiated inner retina as well as in cells occupying the ventricular zone, suggesting that both postmitotic neurons and proliferative progenitors may directly respond to CNTF-like cytokines during postnatal development. The distribution of cytokine signaling pathway components in the adult mouse retina is consistent with previous findings that ganglion cells and Müller glia are the primary target cell types for CNTF.

Animals↗
PubMed1998

RPE secreted proteins and antibody influence photoreceptor cell survival and maturation.

Proteins in media conditioned by retinal pigment epithelial cells (RPE-CM) and an antibody against these proteins (RPE-SP) were tested for their respective effects on rat retinal development in vitro and in vivo. Proteins of RPE-CM were separated in denaturing gels and evaluated by Western blot analysis. Retinal explants from postnatal day 2 (P2) rats were cultured in RPE-CM only or CM diluted with the RPE-SP antibody and, after 7 days, the explants were dissociated into single cells that were immunostained for opsin. RPE-CM or antibody was also injected into the vitreous of postnatal day 7 (P7) Long-Evans rats and analyzed 7 and 21 days later. Electrophoretic analysis of RPE-CM predominantly showed 60-70 kDa proteins; when these proteins were probed with RPE-SP antibody by Western blot, immunoreactive proteins were restricted to this narrow molecular weight range. In P2 retinal explant cultures supplemented with RPE-CM, long ganglion cell-like neurites were detected in 3 days. This activity was nullified in explant cultures grown in RPE-CM titrated with antibody, and these explants appeared to degenerate within 5 days. Over 80% of dissociated retinal cells from explants 7 days after treatment with RPE-CM expressed opsin, compared to only 20% of cells from explants grown in defined medium or serum. Retinas of P14 rats injected intravitreally with RPE-CM at P7 had increased numbers of ectopic photoreceptor cells within the inner nuclear layer when compared to retinas of sham-injected eyes. In contrast, retinas of eyes injected intravitreally with RPE-SP antibody exhibited shorter outer (OS) and inner (IS) segments and thinner outer nuclear (ONL) and outer plexiform (OPL) layers than retinas of sham-injected eyes. In conclusion, proteins in RPE-CM appeared to accelerate and maximize the development of rat photoreceptor cells in vitro, while intravitreal injections of its antibody caused an apparent retardation of outer segment maturation. These results suggest that a protein(s) secreted by RPE plays a key role in normal retinal development, particularly in photoreceptor cell survival and outer segment maturation.

Animals↗
PubMedDate not supplied

Ophthalmic complications after heart transplantation.

To ascertain the ophthalmic complications after heart transplantation, the authors reviewed 59 patients who had been referred to the ophthalmology department during a 4-year period and were subsequently followed for at least 1 year. Twenty-five patients (43%) were found to have lens changes in one or both eyes, which is typical of prolonged oral corticosteroid therapy. In three patients (5.2%) posterior subcapsular cataract formation progressed to a level where cataract surgery was required. In two patients (3.4%) cytomegalovirus retinitis developed within 6 months of the transplantation, and significant irreversible visual loss occurred. Retinal vascular changes were found in 22 patients (37.3%), including 18 patients with hypertensive retinopathy and one patient with background diabetic retinopathy. During the period of observation, a central retinal vein occlusion developed in one patient, an anterior ischemic optic neuropathy developed in one patient, and bilateral occipital lobe infarctions developed in one patient. Older patients and those with a longer survival time after transplantation were more likely to have ophthalmic complications (p = 0.04). Although these results indicate a low incidence of sight-threatening complications after heart transplantation, early referral of patients with visual symptoms is important. Those involved with the care of heart transplant patients should be aware of ocular complications secondary to immune suppression and underlying cardiovascular disease.

Adolescent↗
PubMed1992

Developmental regulation of adenosine A1 receptors, uptake sites and endogenous adenosine in the chick retina.

Although adenosine A1 receptors mediate the inhibition of dopamine-dependent stimulation of adenylate cyclase activity in the developing chick retina, their localization and function are unknown. We have examined the localization of these receptors, and of endogenous adenosine and adenosine uptake sites at several stages of chick retinal development. A1 receptors were already localized predominantly to plexiform regions by embryonic day 12 (E12) with no gross changes at subsequent stages. Adenosine immunoreactivity was absent from retina at E8 but was detected at E12 in the ganglion cell layer, as well as cells in the inner nuclear cell layer and photoreceptors. At more advanced developmental stages the immunoreactivity was greater, but displayed similar localizations. Uptake sites labeled with [3H]nitrobenzylthioinosine (NBI) were detected even earlier using binding and autoradiographic methods. [3H]NBI binding was saturable, and Scatchard analysis demonstrated a single class of sites with a Kd of 0.91 nM and Bmax of 298 fmol/mg protein in E15 retinal membranes. The binding was displaced by unlabeled NBI and dipyridamole. NBI binding sites differentiated earlier than adenosine A1 receptors or endogenous adenosine immunoreactivity, showing a diffuse distribution at E8, but predominating in the plexiform layers of more developed retinas. The results indicate that elements of a putative purinergic system differentiate at specific localizations early in retinal development.

Adenosine↗
PubMed2006

Ontogeny of VEGF, IGF-I, and GH in neonatal rat serum, vitreous fluid, and retina from birth to weaning.

PURPOSE: Vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF)-I, and growth hormone (GH) are major regulators of physical growth, as well as normal and pathologic retinal development. Ocular tissues are protected by the blood-ocular barrier. This study was conducted to test the hypothesis that the ontogenic profiles of VEGF, IGF-I, and GH in the rat serum, vitreous fluid, and retina are compartment specific, and that the vitreous is a reservoir for retinal growth factors. METHODS: Sprague-Dawley rat pups were killed at birth (postnatal day [P]0) and at P7, P14, and P21. At death, serum, vitreous fluid, and retinal homogenates were analyzed for ontogeny of VEGF, IGF-I, and GH. RESULTS: VEGF levels were 10 times higher in the vitreous than in serum at all stages of development. Vitreous and serum VEGF levels progressively declined, with lowest concentrations at P21. Retinal VEGF levels increased with the highest concentration at P21. IGF-I levels in the vitreous decreased from P7 through P21. IGF-I levels in serum and retinal homogenates increased with advancing postnatal age. Although IGF-I levels were four times higher in the vitreous than in the retina at P0, equilibration was achieved at P21. GH levels in the vitreous were 10 times lower than serum levels, were decreased at P14 and P21, and remained unchanged from P0 through P21 in the retina. CONCLUSIONS: VEGF and IGF-I act in concert to promote retinal development with the vitreous fluid as a reservoir. The ontogenic profiles of VEGF, IGF-I and GH in the serum and ocular compartments are specific. These differences should be considered when therapies for ROP are proposed.

Animals↗
PubMed2005

Exposure to diazinon alters in vitro retinogenesis: retinospheroid morphology, development of chicken retinal cell types, and gene expression.

Developing embryos are more vulnerable than adults to acute cholinergic intoxication by anticholinesterases, including organophosphorus pesticides. These agents affect the process of neural development itself, leading to permanent deficits in the architecture of the nervous system. Recent evidence on direct roles of acetylcholinesterase (AChE) on neuronal differentiation provides additional grounds for investigating the developmental toxicity of anticholinesterases. Therefore, the effect of the organophosphate diazinon on the development of chick retinal differentiation was studied by an in vitro reaggregate approach. Reaggregated spheres from dissociated retinal cells of the E6 chick embryo were produced in rotation culture. During the whole culture period of 10 days, experimental cultures were supplemented with different concentrations of the pesticide, from 20 to 120 microM diazinon. The pesticide-treated spheres were reduced in size, and their outer surface was irregular. More importantly, inner structural distortions could be easily traced because the structure of control spheroids can be well characterized by a histotypical arrangement of laminar parts homologous to the normal retina. Acetylcholinesterase activity in diazinon-treated spheres was reduced when compared with controls. As a dramatic effect of exposure to the pesticide, inner plexiform layer (IPL)-like areas in spheroids were not distinguishable anymore. Similarly, photoreceptor rosettes and Müller radial glia were strongly decreased, whereas apoptosis was stimulated. The expression of transcripts for choline-acetyltransferase and muscarinic receptors was affected, revealing an effect of diazinon on the cholinergic system. This further proves the significance of cholinesterases and the cholinergic system for proper nervous system development and shows that further studies of debilitating diazinon actions on development are necessary.

Acetylcholinesterase↗
PubMed1992

[Acute necrotizing retinitis with amotio retinae. Surgical and medicamentous antiviral therapy].

This report pertains to the case of a 25-year-old patient suffering from acute necrotizing retinitis (ANR syndrome). Initially, one eye revealed clinical signs of diffuse chorioretinitis accompanied by perivasculitis and heavy keratic precipitates, papillitis, and vitreous infiltrates. After initial improvement under antiphlogistic therapy, however, necrotizing retinitis developed, associated with peripapillar hemorrhages, multiple peripheral retinal holes and eventually complete retinal detachment. The subsequently performed retinal detachment surgery, completed with vitrectomy, cerclage and silicone oil tamponade, was successful. At the same time, the patient was put on systemic therapy based on acyclovir. In the literature, similar developments are usually related to HSV and HZV infections. Although in our case a virological diagnostic test did not reveal the presence of any virus, the characteristic symptoms of the ANR syndrome completely disappeared under the above-mentioned therapy. Visual acuity, previously consisting only in light perception, improved to 0.4.

Acyclovir↗
PubMed1993

Primary posterior chamber IOL implantation in penetrating ocular trauma.

This paper describes the experience of primary cataract extraction and posterior chamber IOL implantation in 11 eyes with penetrating ocular trauma. The primary surgical procedure consisted of repair of corneoscleral laceration, cataract extraction, posterior chamber IOL implantation and in certain cases, removal of intraocular foreign body and vitrectomy. 10 out of 11 cases had a post operative visual acuity of 6/18 or better, with 9 out of 11 having a post operative visual acuity of 6/12 or better. One case initially had a visual acuity of 6/24 but later developed retinal detachment with a visual acuity of 'hand movements'. Another patient developed a small localised retinal detachment during the tenth postoperative month but with successful surgery, attained a visual acuity of 6/6. The encouraging results suggest that this procedure may be recommended in carefully selected cases, under the management of an experienced surgeon.

Adult↗
PubMed1983

Ophthalmologic safety of long-term hydroxychloroquine sulfate treatment.

The fear of retinal toxicity has been a major factor limiting the use of chloroquine and hydroxychloroquine. Patients reported to develop retinal toxicity with visual loss usually took daily dosages higher than those currently in use. Toxicity with low dosages (for example, 250 mg per day chloroquine or 400 mg per day hydroxychloroquine) usually reveals pigment abnormalities; associated loss of vision is rare. When 99 patients treated with hydroxychloroquine for more than one year were studied prospectively, four patients showed evidence of retinal toxicity; none developed visual loss, and all abnormalities were completely reversible after drug discontinuation. All persons receiving antimalarials should be evaluated by an ophthalmologist at baseline and every six months thereafter. Funduscopic examinations and visual field testing with a red object must be included. Although this protocol may detect abnormalities that are not drug related, no loss of vision has developed in patients so monitored.

Adult↗
PubMed2005

Roles of cell-intrinsic and microenvironmental factors in photoreceptor cell differentiation.

Photoreceptor differentiation requires the coordinated expression of numerous genes. It is unknown whether those genes share common regulatory mechanisms or are independently regulated by distinct mechanisms. To distinguish between these scenarios, we have used in situ hybridization, RT-PCR, and real-time PCR to analyze the expression of visual pigments and other photoreceptor-specific genes during chick embryo retinal development in ovo, as well as in retinal cell cultures treated with molecules that regulate the expression of particular visual pigments. In ovo, onset of gene expression was asynchronous, becoming detectable at the time of photoreceptor generation (ED 5-8) for some photoreceptor genes, but only around the time of outer segment formation (ED 14-16) for others. Treatment of retinal cell cultures with activin, staurosporine, or CNTF selectively induced or down-regulated specific visual pigment genes, but many cognate rod- or cone-specific genes were not affected by the treatments. These results indicate that many photoreceptor genes are independently regulated during development, are consistent with the existence of at least two distinct stages of gene expression during photoreceptor differentiation, suggest that intrinsic, coordinated regulation of a cascade of gene expression triggered by a commitment to the photoreceptor fate is not a general mechanism of photoreceptor differentiation, and imply that using a single photoreceptor-specific "marker" as a proxy to identify photoreceptor cell fate is problematic.

Activins↗
PubMed1999

Discontinuation of anticytomegalovirus therapy in patients with HIV infection and cytomegalovirus retinitis.

CONTEXT: Persons with cytomegalovirus (CMV) retinitis and acquired immunodeficiency syndrome (AIDS) have required lifelong anti-CMV therapy to prevent the progression of retinal disease and subsequent loss of vision. OBJECTIVE: To determine whether patients who were taking highly active antiretroviral therapy (HAART) and who had stable CMV retinitis could safely discontinue anti-CMV therapy without reactivation of their retinitis or increase in human immunodeficiency virus (HIV) viral load. DESIGN: Prospective nonrandomized interventional trial performed from July 1997 to August 1999. SETTING: Clinical Center of the National Institutes of Health, Bethesda, Md. PATIENTS: Fourteen patients with stable CMV retinitis and HIV infection and CD4+ cell counts higher than 0.1 5 x 10(9)/L and being treated with systemic anti-CMV medications and HAART. INTERVENTIONS: Discontinuation of specific anti-CMV therapy. MAIN OUTCOME MEASURES: Reactivation of CMV retinitis, development of extraocular CMV infection, detection of CMV in blood and urine, HIV burden, immunologic function, quality of life, morbidity, and mortality. RESULTS: Twelve (89.7%) of 14 patients had evidence of immune recovery uveitis before anti-CMV drugs were discontinued. No patient had reactivation of CMV retinitis or development of extraocular CMV disease during mean follow-up of 16.4 months (range, 8.3-22.0 months) without anti-CMV therapy. Human immunodeficiency viral load remained stable following cessation of anti-CMV medications. Blood and urine assays for CMV were briefly positive in 9 patients but did not predict reactivation of CMV disease. Worsening immune recovery uveitis was associated with a substantial (>3 lines) vision loss in 3 patients. CONCLUSIONS: Maintenance anti-CMV medications were safely stopped in those patients who had stable CMV retinitis and elevated CD4+ cell counts and who were taking HAART. The study demonstrates that immune recovery following potent antiretroviral therapy is effective in controlling a major opportunistic infection, even in patients with a history of severe immunosuppression.

AIDS-Related Opportunistic Infections↗
PubMed2000

Kinase independent function of EphB receptors in retinal axon pathfinding to the optic disc from dorsal but not ventral retina.

Optic nerve formation requires precise retinal ganglion cell (RGC) axon pathfinding within the retina to the optic disc, the molecular basis of which is not well understood. At CNS targets, interactions between Eph receptor tyrosine kinases on RGC axons and ephrin ligands on target cells have been implicated in formation of topographic maps. However, studies in chick and mouse have shown that both Eph receptors and ephrins are also expressed within the retina itself, raising the possibility that this receptor-ligand family mediates aspects of retinal development. Here, we more fully document the presence of specific EphB receptors and B-ephrins in embryonic mouse retina and provide evidence that EphB receptors are involved in RGC axon pathfinding to the optic disc. We find that as RGC axons begin this pathfinding process, EphB receptors are uniformly expressed along the dorsal-ventral retinal axis. This is in contrast to the previously reported high ventral-low dorsal gradient of EphB receptors later in development when RGC axons map to CNS targets. We show that mice lacking both EphB2 and EphB3 receptor tyrosine kinases, but not each alone, exhibit increased frequency of RGC axon guidance errors to the optic disc. In these animals, major aspects of retinal development and cellular organization appear normal, as do the expression of other RGC guidance cues netrin, DCC, and L1. Unexpectedly, errors occur in dorsal but not ventral retina despite early uniform or later high ventral expression of EphB2 and EphB3. Furthermore, embryos lacking EphB3 and the kinase domain of EphB2 do not show increased errors, consistent with a guidance role for the EphB2 extracellular domain. Thus, while Eph kinase function is involved in RGC axon mapping in the brain, RGC axon pathfinding within the retina is partially mediated by EphB receptors acting in a kinase-independent manner.

Animals↗
PubMed1997

Risk for retinitis in patients with AIDS can be assessed by quantitation of threshold levels of cytomegalovirus DNA burden in blood.

Cytomegalovirus (CMV) retinitis in patients infected with human immunodeficiency virus (HIV) is a significant clinical problem. Seventy-five patients with CD4 T cell counts <100/mm3 were monitored prospectively every 2 months for CMV DNA burden. The target for DNA amplification was a 162-bp fragment from the CMV immediate early gene. CMV DNA burden, at levels of > or =320 in white blood cells or > or =32 in plasma (P = .001), particularly when sustained (P = .005 and .008, respectively), distinguished patients who developed retinitis from those who remained free of disease. Progression to retinitis was not consistently accompanied by increases in CMV burden, indicating that quantitation of CMV burden beyond threshold levels is not necessary to predict risk for development of retinitis. Virus isolation from WBC, but not urine, was also significantly associated with risk for retinitis (P = .001).

Acquired Immunodeficiency Syndrome↗
PubMed2004

Multipotent retinal progenitors express developmental markers, differentiate into retinal neurons, and preserve light-mediated behavior.

PURPOSE: To use progenitor cells isolated from the neural retina for transplantation studies in mice with retinal degeneration. METHODS: Retinal progenitor cells from postnatal day 1 green fluorescent protein-transgenic mice were isolated and characterized. These cells can be expanded greatly in culture and express markers characteristic of neural progenitor cells and/or retinal development. RESULTS: After they were grafted to the degenerating retina of mature mice, a subset of the retinal progenitor cells developed into mature neurons, including presumptive photoreceptors expressing recoverin, rhodopsin, or cone opsin. In rho-/- hosts, there was rescue of cells in the outer nuclear layer (ONL), along with widespread integration of donor cells into the inner retina, and recipient mice showed improved light-mediated behavior compared with control animals. CONCLUSIONS: These findings have implications for the treatment of retinal degeneration, in which neuronal replacement and photoreceptor rescue are major therapeutic goals.

Animals↗
PubMed1998

Induction of alpha1-tubulin gene expression during development and regeneration of the fish central nervous system.

The alpha1- and alpha2-tubulin encoding genes were cloned from a goldfish genomic DNA library. alpha1- and alpha2-tubulin RNA expression was examined in developing and adult retinas. These studies demonstrated increased alpha1-tubulin RNA in presumptive ganglion cells that grow axons early in retinal development and in adult retinal ganglion cells whose optic axons had been damaged. The alpha2-tubulin RNA was undetectable in developing retina and constitutively expressed in adult retinal ganglion cells regardless of optic nerve crush. To determine if these changes in alpha1-tubulin RNA reflected changes in alpha1-tubulin promoter activity, we introduced into zebrafish embryos and adult goldfish retinal explants expression vectors harboring the alpha1-tubulin gene's promoter. These studies showed that the alpha1-tubulin promoter confers a developmentally regulated, neuron-restricted pattern of reporter gene expression in vivo and its activity is increased in adult retinal neurons induced to regenerate their axons. Promoter deletions defined regions of alpha1-tubulin DNA necessary for this pattern of expression. These results suggest that DNA sequences necessary for alpha1-tubulin gene induction during central nervous system development and regeneration are contained within the alpha1-tubulin gene's 5'-flanking DNA and that this promoter will be useful for identifying these elements and their DNA binding proteins.

Animals↗
PubMed2004

Tbx12 regulates eye development in Xenopus embryos.

The regulation of vertebrate eye development requires the activity of many transcription factors. In this report, we demonstrate that the T-box factor Tbx12 is necessary for normal development of the retina. Tbx12 is expressed during early stages of retinal development in multiple species of vertebrate embryos. We injected mRNAs encoding wild type and mutant forms of Tbx12 into Xenopus embryos. The Tbx12 injected embryos exhibit multiple defects in eye development including reduced eye size and disruption of normal retinal laminar organization. Tbx12 appears to function as a repressor of transcription during eye development. Our results indicate that Tbx12 activity is required for the proper generation and organization of retinal cells in the vertebrate eye.

Animals↗