Neuropharmacological characterization of basal forebrain cholinergic stimulated cataplexy in narcoleptic canines

Bacterial collagenase was injected into the vitreous of the eye of chick and quail embryos. Immunocytochemical and ultrastructural studies revealed that the collagenase dissolved the retinal basal lamina of the injected eye. The basal lamina disruption was first detectable 1 hour after enzyme injection and was complete within 3 hours. With further development, the retinal basal lamina was not reestablished; newly developing neuroepithelium in the peripheral retina, however, generated an intact basal lamina. Western blot analysis showed that Clostridial collagenase degraded various collagens but spared noncollagenous proteins. Basal lamina disruption of embryonic day 3 to 6 retinae led to the retraction of the end feet of the neuroepithelial cells, caused an increase in the number of Islet-1+ cells (most likely ganglion cells), an increase in the thickness of the optic fiber layer, and aberrant growth of optic axons on their way toward the optic disc. None of these changes were observed when retinal basal laminae were disrupted at later stages of development. The present data demonstrate that the retinal basal lamina, by anchoring the neuroepithelial cells to the pial surface of the retina, has an important function in the development of the normal cytoarchitecture of this structure. It is proposed that the altered extracellular environment in the vitreal part of the retina, resulting in the retraction of the neuroepithelial end feet, is responsible for the increased number of Islet-1+ cells and the aberrant axonal navigation.     

Ischemic optic neuritis in Churg-Strauss syndrome

There are few reports of neuro-ophthalmologic involvement in Churg-Strauss syndrome (CSs). We described a case of unilateral optic atrophy in a 46-year-old-white man with CSs. The patient had severe bronchial asthma, allergic rhinitis, hypereosinophilia (8%) and peripheral neuropathy. The visual acuity in his right eye was light perception. At the biomicroscopy there were no corneal and conjunctival lesions. Ophthalmoscopy showed a pale right optic disc and fluorangiography revealed a marked hypofluorescence of the disc at early phase of angiogram. We suggested that the optic atrophy was most probably due to vasculitis of the ciliary arteries.     

Dendritic field development of retinal ganglion cells in the cat following neonatal damage to visual cortex: evidence for cell class specific interactions

A well-known feature of the mammalian retina is the inverse relation that exists in central and peripheral retina between the density of retinal ganglion cells and their dendritic field sizes. Functionally, this inverse relation is thought to represent a means by which retinal coverage is maintained, despite significant changes in ganglion cell density. While it is generally agreed that the dendritic fields of mature retinal ganglion cells reflect, in part, competitive interactions that occur during development, the issue of whether these interactions are cell class specific remains unclear. In order to examine this question, we used intracellular staining techniques and an in vitro, living retina preparation to compare the soma and dendritic field sizes of alpha and beta ganglion cells from normal retinae with those of cells located in matched areas of retinae in which the density of beta ganglion cells had been reduced selectively by neonatal removal of visual cortex areas 17, 18, and 19. Our intracellular data show that while an early, selective, reduction in beta cell density has little or no effect on the cell body and dendritic field sizes of mature alpha cells, it results in a 13% increase in the mean soma area and an 83% increase in the mean dendritic field area of surviving beta cells. This differential effect suggests that the soma and dendritic field sizes of alpha and beta ganglion cells in the mature cat retina result primarily from competitive interactions during development that are cell class specific.     

Bilateral disc edema in retinitis pigmentosa

Retinitis pigmentosa (RP), one of the most common forms of hereditary retinal degeneration, is characterized by night blindness and constricted visual fields. In addition to bone spicule pigmentation, other ocular findings may include posterior subcapsular cataracts, cystoid macular edema, and hyaline bodies or drusen of the optic nerve. Rarely, optic nerve head (ONH) edema has been reported to be associated with RP. A 44-year-old white male with RP and neurosensory hearing loss (Usher's syndrome type II) presented to our clinic for routine examination. A dilated fundus examination revealed bone spicule pigmentation, vessel attenuation, several flame hemorrhages on or adjacent to the nerves, and ONH edema in the right eye. B-scan ultrasonography revealed drusen of the right ONH but not of the left. Late stage fluorescein angiography showed hyperfluorescence and dye leakage from both optic discs which was more pronounced in the right eye than the left. Computed tomography (CT) of the head and orbits and cerebrospinal fluid (CSF) examination by lumbar puncture were normal. The differential diagnosis of bilateral ONH edema in this case included ONH drusen or papilledema secondary to increased intracranial pressure. This patient was found to have RP with asymmetric, bilateral ONH edema of unknown cause. One theory regarding the cause of the ONH edema is disc vessel leakage secondary to an inflammatory reaction caused by rapid photoreceptor and retinal pigment epithelium (RPE) degeneration.     

The eyes of deep-sea fish. II. Functional morphology of the retina

Three different aspects of the morphological organisation of deep-sea fish retinae are reviewed: First, questions of general cell biological relevance are addressed with respect to the development and proliferation patterns of photoreceptors, and problems associated with the growth of multibank retinae, and with outer segment renewal are discussed in situations where there is no direct contact between the retinal pigment epithelium and the tips of rod outer segments. The second part deals with the neural portion of the deep-sea fish retina. Cell densities are greatly reduced, yet neurohistochemistry demonstrates that all major neurotransmitters and neuropeptides found in other vertebrate retinae are also present in deep-sea fish. Quantitatively, convergence rates in unspecialised parts of the retina are similar to those in nocturnal mammals. The differentiation of horizontal cells makes it unlikely that species with more than a single visual pigment are capable of colour vision. In the third part, the diversity of deep-sea fish retinae is highlighted. Based on the topography of ganglion cells, species are identified with areae or foveae located in various parts of the retina, giving them a greatly improved spatial resolving power in specific parts of their visual fields. The highest degree of specialisation is found in tubular eyes. This is demonstrated in a case study of the scopelarchid retina, where as many as seven regions with different degrees of differentiation can be distinguished, ranging from an area giganto cellularis, regions with grouped rods to retinal diverticulum.     

Seven retinal specializations in the tubular eye of the deep-sea pearleye, Scopelarchus michaelsarsi: a case study in visual optimization

The deep-sea pearleye, Scopelarchus michaelsarsi (Scopelarchidae) is a mesopelagic teleost with asymmetric or tubular eyes. The main retina subtends a large dorsal binocular field, while the accessory retina subtends a restricted monocular field of lateral visual space. Ocular specializations to increase the lateral visual field include an oblique pupil and a corneal lens pad. A detailed morphological and topographic study of the photoreceptors and retinal ganglion cells reveals seven specializations: a centronasal region of the main retina with ungrouped rod-like photoreceptors overlying a retinal tapetum; a region of high ganglion cell density (area centralis of 56.1 x 10(3) cells per mm2) in the centrolateral region of the main retina; a centrotemporal region of the main retina with grouped rod-like photoreceptors; a region (area giganto cellularis) of large (32.2+/-5.6 microm2), alpha-like ganglion cells arranged in a regular array (nearest neighbour distance 53.5+/-9.3 microm with a conformity ratio of 5.8) in the temporal main retina; an accessory retina with grouped rod-like photoreceptors; a nasotemporal band of a mixture of rod- and cone-like photoreceptors restricted to the ventral accessory retina; and a retinal diverticulum comprised of a ventral region of differentiated accessory retina located medial to the optic nerve head. Retrograde labelling from the optic nerve with DiI shows that approximately 14% of the cells in the ganglion cell layer of the main retina are displaced amacrine cells at 1.5 mm eccentricity. Cryosectioning of the tubular eye confirms Matthiessen's ratio (2.59), and calculations of the spatial resolving power suggests that the function of the area centralis (7.4 cycles per degree/8.1 minutes of arc) and the cohort of temporal alpha-like ganglion cells (0.85 cycles per degree/70.6 minutes of arc) in the main retina may be different. Low summation ratios in these various retinal zones suggests that each zone may mediate distinct visual tasks in a certain region of the visual field by optimizing sensitivity and/or resolving power.     

Sensitivities of ocular tissues to acute pressure-induced ischemia

Intraocular pressure was artificially elevated for eight hours in eight owl monkeys. The first permanent effect (produced at a perfusion pressure of plus 15 mm Hg) was partial necrosis of iris stroma and ciliary processes, associated with microscopic lesions in the photoreceptors and retina pigment epithelium around the disc and in the retinal periphery. At a slightly higher pressure, visual nerve fibers in the retina and optic nerve and their ganglion cells were affected. Simultaneously, the outer retinal layers showed damage to the pigment epithelium, photoreceptors, and other nuclear layers. At even higher pressures, nearly all the other intraocular tissues were affected except for Müller cells, astroglia in the optic nerve head, epithelium of the pars plana, and the pigment cells of the choroid. The possibility is raised of a nonischemic pressure-induced mechanism for destruction of disc astrocytes in human chronic glaucoma.     

Transient neovascularisation of the frog retina during optic nerve regeneration

In conditions such as diabetic retinopathy, degenerative events in the retina are associated with neovascularisation. It is well established that a proportion of retinal ganglion cells die during optic nerve regeneration in the frog. The present study has determined whether neovascularisation takes place during this regenerative process. To do so, the pattern of blood vessels overlying the retinal ganglion cell layer was analysed in the frog Litoria (Hyla) moorei. We examined normal animals and those undergoing optic nerve regeneration following nerve crush. Blood vessels were visualised by perfusion with Indian ink and retinae were prepared as wholeamounts. In normal animals, the vascular tree was found to lie superficial to the nerve fibre layer and was more complex in regions overlying the area centralis and visual streak. After nerve crush, abnormal blood vessels transiently formed between the existing branches of the vascular tree. The new vessels were concentrated as an annulus centred on the optic nerve head and over the area centralis in midtemporal retina. The neovascularisation became most extensive between 6 and 10 weeks postcrush and disappeared by 12 weeks. The spatiotemporal sequence of neovascularisation suggests that it is triggered by accumulations of degenerating material formed as a proportion of the ganglion cells die during optic nerve regeneration.     

A case of nonarteritic anterior ischemic optic neuropathy with cilioretinal artery occlusion

We report a case of nonarteritic anterior ischemic optic neuropathy (AION) with cilioretinal artery occlusion. The patient was a 61-year-old man with sudden visual loss in his right eye. Funduscopy showed pale swelling of the entire optic disc with retinal ischemic edema of the upper half of the retina, and fluorescein angiography revealed faint filling of the dye in the optic disc in the retinal arterial phase, and dye staining of the optic disc in the late phase. We initially diagnosed the disease as AION with branch retinal artery occlusion, but systemic administration of a corticosteroid and urokinase were ineffective and the optic disc became atrophic. As the optic disc swelling decreased and the course of arteries in the optic disc became clear, we repeated fluorescein angiography which proved that the involved upper retinal artery was a cilioretinal artery having earlier dye appearance than the lower retinal artery. Thus, we finally diagnosed the disease as AION with cilioretinal artery occlusion. We believe that Hayreh's view that AION may result from occlusion of the posterior ciliary artery is supported by the intraocular findings in this case.     

HTLV-I associated myelopathy with macular degeneration

The authors report a case of macular involvement in a patient with HTLV-I associated myelopathy (HAM). The patient was a 10-year-old girl who noticed sudden decreased vision in her right eye in November 1987. The corrected visual acuity was 0.01 in the right eye and 1.0 in the left eye. Fundus examination of the right eye disclosed mild optic disc pallor. The macula appeared to have pigmentary mottling with superficial irregular retinal reflex that was three disc diameters in size. Fluorescein angiography revealed a discoid hypofluorescent area in the macula, surrounded by mottled hyperfluorescent areas. She had no contributory family history of ocular disease, but had a history of blood transfusion during an operation for patent ductus arteriosus and ventricular septal defect at the age of 8 months. In November 1990, she developed gait disturbance due to spastic paraparesis and was admitted to our hospital. Antibodies to HTLV-I were markedly elevated in serum (titer, 1:8192) and in cerebrospinal fluid (titer, 1: 1024). She was diagnosed as HAM. Two months later, she developed encephalopathy and bilateral optic disc atrophy.     

Defective phagocytosis in systemic lupus erythematosus

The authors describe a case of traumatic retinal dialysis with retinal detachment from a water balloon slingshot during a "water balloon war." A 31-year-old woman presented with decreased visual acuity in her right eye 2 days after being hit by a water balloon. The visual acuity in the right eye was counting fingers and fundus examination showed subtotal retinal detachment secondary to a superonasal dialysis. The patient underwent a scleral buckling procedure with external drainage, and at 18 months visual acuity was stable at 20/50 with attached retina. Water balloon eye injuries can result in permanent visual loss. More public awareness needs to be created regarding the potential harmful effects of this commonly used "toy."     

Rod outer segment renewal in the retinae of deep-sea fish

Outer segment renewal involves the synthesis of disc material in the photoreceptor inner segments, the shedding of the tips of the photoreceptor outer segments, and their phagocytosis by the retinal pigment epithelial cells. It has been suggested that in the retinae of deep-sea fish no renewal of outer segments may take place. In order to assess outer segment renewal in deep-sea fish retinae we counted (i) periciliary vesicles in rod inner segments as a parameter for disc-synthesis activity and (ii) phagosomes in retinal pigment epithelial cells as a parameter of shedding and phagocytosis in 12 species of deep-sea fish with multibank or single bank retinae. We also measured the lengths of rod outer segments in order to evaluate the balance between synthesis and phagocytotic activity. In four of these species (Synaphobranchus kaupi, Nematonurus armatus, Coryphaenoides guentheri and Halosauropsis macrochir) we further recorded size-related changes of these parameters and their relation to the position of a given rod within the banks in the retina. The number of periciliary vesicles was highest in inner segments of the most vitread bank and in the periphery of the retina. Phagosomes were most abundant in retinal pigment epithelial cells of the central retina. Long rod outer segments were most frequently recorded in the peripheral retina indicating that in this region new synthesis may outbalance shedding. Vitread rod outer segments were only slightly longer than sclerad ones. Larger animals had shorter rod outer segments than small ones. We present evidence that rod outer segment renewal takes place in the retina of all deep-sea fish. Vitread rods may be more active in this respect than sclerad ones.     

Diagnosis and therapy of antiphospholipid antibody syndrome

PURPOSE: To report alterations of electrophysiologic tests, including the multifocal electroretinogram, in a case of acute zonal occult outer retinopathy. METHOD: We recorded photopic, scotopic, and single-flash electroretinograms and a multifocal electroretinogram in a 47-year-old woman with acute zonal occult outer retinopathy in the right eye. RESULTS: Her visual acuity was 20/20 in the right eye throughout the follow-up period. The electroretinograms indicated retinal impairment of the right eye, predominantly in the cones. The multifocal electroretinogram showed reduced responses corresponding to the visual field defect of the static perimetry. CONCLUSIONS: In acute zonal occult outer retinopathy, impairment of the retinal area results in a visual field defect. The multifocal electroretinogram can be useful in determining the location of the defect.     

Anxiety and cognitive performance in adolescent women with disruptive behavior disorders

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific angiogenic and permeability-inducing factor that has been implicated in the pathogenesis of diabetic retinopathy. In the present study, the localization and magnitude of VEGF, VEGF receptor-1 (VEGFR-1), and VEGF receptor-2 (VEGFR-2) gene expression were examined in the eye of streptozotocin-induced diabetic rats using quantitative in situ hybridization. VEGF protein was also examined by immunohistochemistry. Abundant VEGF mRNA and protein were present in the retinae of control rats. In the retinae of diabetic rats, VEGF gene expression was increased compared with control animals (p = 0.001). The increase in VEGF mRNA was noted in the ganglion cell layer and inner nuclear layer but not in the pigment epithelium of the retina. VEGF was also detected in blood vessels, ciliary body, and lens epithelium in both control and diabetic rats. The distributions of VEGFR-1 and VEGFR-2 were similar in both control and diabetic rats. VEGFR-1 mRNA was present beneath the inner limiting membrane and in the ganglion cell layer, inner nuclear layer, outer plexiform layer, and outer limiting membrane of the retina; it was also detected in blood vessels, the ciliary body, and the cornea. The magnitude and distribution of ocular VEGFR-1 mRNA were not affected by experimental diabetes. Expression of VEGFR-2 mRNA was noted in the inner nuclear layer and pigment epithelium of the retina and in blood vessels. An increase in VEGFR-2 mRNA in the diabetic retina was restricted to the inner nuclear layer. The presence of VEGF and its receptors in the control retina suggests a physiologic role for VEGF within the eye. The changes in retinal expression of VEGF and VEGFR-2 in association with diabetes suggest a role for this pathway in diabetic retinopathy.     

Intraocular silicone oil tamponade. A clinico-pathologic study of 36 enucleated eyes

BACKGROUND: Previous histological studies have shown that intraocular silicone oil induces irreversible changes in ocular tissues, especially the retina. The purpose of this study was to analyze, in a larger group of enucleated eyes, changes in intraocular tissue after silicone oil injection, dependent on intraocular pressure, how long the oil was in the eye, and the viscosity of intraocular silicone oil. PATIENTS AND METHODS: We did histological examinations on 36 enucleated globes with intraocular silicone oil after vitreoretinal surgery and compared them with 68 enucleated globes treated with buckle and encircling band using immunohistochemistry (n = 5) and electron microscopy (n = 7). For statistical evaluation we used the chi(2) test and analysis of variance. RESULTS: After silicone oil injection we observed a more pronounced reduction in corneal endothelial cells (58%), more frequent closed chamber angle (86%), atrophy of the ciliary body (80%) (P < 0.05), proliferative vitreoretinopathy (89%), and glaucomatous atrophy of the optic nerve (56%) (P < 0.01). The retinae showed independent of the use of silicone oil a loss of inner and outer segments of photoreceptors and of ganglion cells and thinning and rareficaton of all other retinal layers. Globes with silicone oil revealed vacuoles both free and incorporated by macrophages in all layers of the retina. Similar vacuoles were seen in the optic nerve, choroid, retinal pigment epithelium, ciliary body, iris, chamber angle and the corneal endothelium. Silicone oil vacuoles were seen in the retina and optic nerve by 1 month after surgery in two eyes with high intraocular pressure (42 mmHg). Six of eight eyes with normal intraocular pressure levels showed retinal vacuoles, 3 of them after 2 months. Vacuoles in the optic nerve were found in eight of nine eyes with intraocular instillation of 1000 mPa silicone oil. There was no clinicohistopathological correlation between the presence of vacuoles in the retina or optic nerve and the duration and viscosity of intraocular silicone oil. CONCLUSIONS: This study suggests that vacuoles in eyes with silicone oil instillation can be found in the retina after 4 weeks. The period of intraocular silicone oil should be limited to 3-6 months.     

Equivalence in periodontal trials: a description for the clinician

AIMS: To describe the clinical picture and electrophysiological findings in Müller cell sheen dystrophy, a recently reported retinal dystrophy. METHOD: A basic ophthalmological evaluation as well as recording of standard electro-oculography and electroretinography were performed in one patient at the onset of visual loss and after 1 year of follow up. RESULTS: A 61 year old woman presented with visual loss in the right eye. Multiple folds at the level of the internal limiting membrane were seen at the posterior pole in both eyes. Macular oedema was present in the right eye. The visual acuity of the right eye was 6/30 and of the left 6/9. A paracentral scotoma was found in the right eye. Electro-oculographic examination of both eyes gave normal results. Electroretinography (ERG) revealed reduced b-wave and flicker amplitudes in the right eye; these potentials were normal for the left eye. The ON response in the right eye was reduced and delayed; it was normal in the left eye. A further loss of visual function was noted 1 year later in the right eye, but the ophthalmoscopic findings were unchanged. The ERG of the right eye had a negative waveform when dark adapted. Light adapted responses showed an unusual delayed b-wave, broad and delayed ON and OFF responses and a missing flicker response, suggesting a Müller cell dysfunction. Light adapted responses were slightly reduced in the left eye. CONCLUSIONS: Electrophysiological data indicate Müller cell dysfunction as a background of functional loss in Müller cell sheen dystrophy. This is in agreement with previously reported histological findings in this disorder.     

Choroidal nonperfusion in giant cell arteritis

A 68-year-old man had visual loss secondary to isolated choroidal nonperfusion as a clinical manifestation of giant cell arteritis. Ophthalmoscopy disclosed scattered yellow-white lesions at the level of the retinal pigment epithelium in the posterior pole of the right eye. Intravenous fluorescein angiography demonstrated marked delay in choroidal filling of the macula in the right eye. There was no ophthalmoscopic or angiographic evidence of anterior ischemic optic neuropathy or central retinal artery occlusion. After approximately 72 hours of intravenous corticosteroid therapy, the patient's visual acuity improved and repeat intravenous fluorescein angiography showed normal choroidal circulation. Isolated choroidal ischemia is a potential cause of reversible visual loss in patients with giant cell arteritis.     

Ruthenium-106 brachytherapy for peripheral retinal capillary hemangioma

OBJECTIVE: This study aimed to evaluate the efficacy and safety of ruthenium-106 brachytherapy of large peripheral retinal capillary hemangiomas. DESIGN: A retrospective case series. PARTICIPANTS: In 25 eyes of 24 patients, peripheral capillary retinal hemangiomas were treated. INTERVENTION: Brachytherapy using 106-ruthenium/106-rhodium plaques was performed. MAIN OUTCOME MEASURES: Eyes were reviewed for hemangioma regression after brachytherapy, occurrence of retinal detachment, requirement of additional vitreoretinal surgery, final visual outcome, and final retinal status. RESULTS: Preoperative mean visual acuity of all eyes treated was 20/60, mean hemangioma diameter was 3.8 mm, corresponding to approximately 2 disc diameters. In 14 eyes, the retina was attached before surgery, 8 eyes showed an exudative detachment, and 3 eyes showed a traction detachment. Fifteen patients had definite von Hippel-Lindau syndrome. Twenty-three of 25 hemangiomas could be destroyed by single brachytherapy. In 16 eyes, a favorable outcome could be achieved. In nine eyes, outcome was unfavorable, characterized by a severe drop in visual acuity, a persisting exudative retinal detachment, or a recurrent traction detachment. In one eye requiring repeated brachytherapy, irradiation retinopathy occurred. Hemangiomas up to a size of approximately 5.0 mm without preoperative exudative detachment could be treated safely by brachytherapy, whereas a larger hemangioma size or a pre-existing exudative retinal detachment predisposed to an unfavorable outcome. CONCLUSION: Solitary peripheral retinal hemangioma can be ablated effectively by ruthenium-106 brachytherapy. A favorable outcome can be expected if the hemangioma diameter is 5.0 mm or smaller and if there is no preoperative exudative retinal detachment.     

Effect of strength training on EMG of human skeletal muscle

An 8-year-old white girl with a history of vertigo, nausea, and vomiting developed a progressive hearing loss, bilateral retinal arteriolar narrowing in each eye, vasoproliferation, and subsequent intravitreal hemorrhage. An attempt at peripheral retinal ablation with cryotherapy in the left eye resulted in retinal detachment. Spontaneous retinal detachment occurred in the right eye and was successfully repaired. Repeated intermittent hemorrhages occurred despite intraocular diathermy. Three years after onset, visual acuity was R.E.: 6/21 (20/66) and L.E.: light perception. She remains totally deaf. A 20-year-old white woman developed severe bilateral sensorineural hearing loss with poorly functioning labyrinths, followed by midperipheral retinal arteriolar occlusions and vasoproliferation on the optic nerve head. Progressive retinal neovascularization was followed by rubeosis iridis and repeated episodes of intravitreal bleeding. Six years after onset, visula acuity was R.E.: hand motions, and L.E.: 6/3 (20/100). She remains totally deaf. Both patients were of normal gestation, development, and mentality, without evidence of other systemic disease. The cause of this disease was not found.     

Maturational gradients in the retina of the ferret

In the present set of studies, we have examined the site for the initiation of retinal maturation in the ferret. A variety of maturational features across the developing inner and outer retina were examined by using standard immunohistochemical, carbocyanine dye labelling, and Nissl-staining techniques, including 1) two indices of early differentiation of the first-born retinal ganglion cells, the presence of beta-tubulin and of neuron-specific enolase; 2) the receding distribution of chondroitin sulfate proteoglycans within the inner retina; 3) the distribution of the first ganglion cells to grow axons along the optic nerve; 4) the emergence of the inner plexiform layer; 5) the emergence of the outer plexiform layer and 6) the onset of synaptophysin immunoreactivity within it; 7) the differentiation of calbindin-immunoreactive horizontal cells; and 8) the cessation of proliferative activity at the ventricular surface. Although we were able to define distinct maturational gradients that are associated with many of these features of inner and outer retinal development (each considered in detail in this report), with dorsal retina maturing before ventral retina, and with peripheral retina maturing last, none showed a clear initiation in the region of the developing area centralis. Rather, maturation began in the peripapillary retina dorsal to the optic nerve head, which is consistent with previous studies on the topography of ganglion cell genesis in the ferret. These results make clear that the order of retinal maturation and the formation of the area centralis are not linked, at least not in the ferret.