Time-Dependent Effects of Reduced Cerebrospinal Fluid Pressure on Optic Nerve Retrograde Axonal Transport.

Purpose: To study the time-dependent effects of reduced cerebrospinal fluid pressure (CSFP) on axonal transport in the rat optic nerve. Methods: Seventy-two adult Sprague Dawley rats were used for this study. Fluoro-Gold was injected into the superior colliculi to study axonal transport. CSFP was reduced to 1.5 to 2.9 mm Hg by continuous aspiration of cerebrospinal fluid. In the sham control group (n = 18), a trocar was implanted in the cisterna magna, but cerebrospinal fluid was not released. CSFP and intraocular pressure (IOP) were continually monitored. CSFP was reduced for 1 hour (low-CSFP-1h study group; n = 18), 3 hours (low-CSFP-3h study group; n = 18), or 6 hours (low-CSFP-6h study group; n = 18) before the animals were euthanized. Confocal microscopy was used to compare axonal transport in different quadrants of the retina between control and low-CSFP eyes. Results: Changes in axonal transport were observed only after 3 hours of CSFP reduction and not in the low-CSFP-1h study group. These changes occurred in a time-dependent manner, with 6 hours of CSFP reduction producing the longest lasting and most severe reduction in fluorescence. Conclusions: The time-dependent changes observed in axonal transport in the optic nerve provide further evidence regarding the pathogenesis of axonal damage caused by reduced CSFP.

Assessment of macular function in patients with idiopathic Epiretinal membrane by multifocal Electroretinography: correlation with visual acuity and optical coherence tomography.

BACKGROUND: This study evaluates the macular function changes in patients with idiopathic macular epiretinal membrane (ERM) by multifocal electroretinography (mfERG) and their correlations with visual acuity and central macular thickness (CMT) by optical coherence tomography (OCT). METHODS: Twenty eyes of 20 patients with ERM underwent OCT and mfERG examinations. The response amplitude densities and implicit times of mfERG were compared to the control fellow eyes. Correlation analyses among visual acuity, central macular thickness and mfERG values in the central two concentric rings were performed. RESULTS: The mfERG P1 response amplitude densities in ring 1-2 and P1 implicit time in ring1 were significantly changed in epiretinal membrane eyes compared with controls (P < 0.05). Multivariate stepwise linear regression analyses showed LogMAR visual acuity was significantly correlated with CMT (P = 0.004), and also with the P1 amplitude density in ring 1 (P = 0.002). CMT showed significant correlation with P1 implicit time in ring 2 (P = 0.013). CONCLUSIONS: The mfERG abnormalities show macular function changes and correlate with visual acuity and central macular thickness in eyes with ERM. In first-order mfERG responses, P1 wave changes may be a sensitive functional measurement for ERM patients.

Partial Optic Nerve Transection in Rats: A Model Established with a New Operative Approach to Assess Secondary Degeneration of Retinal Ganglion Cells.

Previous studies have shown that the secondary degeneration of retinal ganglion cells (RGCs) occurs commonly in glaucoma. Partial optic nerve transection is considered a useful and reproducible model. Compared with other optic nerve injury models used commonly for assessing secondary degeneration, e.g. complete optic nerve transection and optic nerve crush models, the partial optic nerve transection model is superior as it distinguishes primary from secondary degeneration in situ. Therefore, it serves as an excellent tool for evaluating secondary degeneration. This study describes a novel operative approach of partial optic nerve transection by directly accessing the area of the retrobulbar optic nerve through the orbital lateral wall of the eyeball. Moreover, we present a newly designed, low cost surgical instrument to assist with transection. As demonstrated by the representative results in distinguishing the boundary of primary and secondary injury areas, the new approach and instrument ensures high efficiency and stability of the model by providing adequate space for surgical operation. This in turn makes it easy to separate the meningeal sheath and ophthalmic vessels from the optic nerve before transection. An additional benefit is that this space-saving operative approach improves the investigators' ability to administer drugs, carriers, or selective RGC tracers to the stump of the partially transected optic nerve, allowing the exploration of mechanisms behind secondary injury in RGCs, in a new way.

Reduction on OFF-responses of Electroretinogram in Monkeys with Long-term High Intraocular Pressure.

BACKGROUND: There are ON- and OFF-pathways in the normal vertebrate retina. Short- and long-flash electroretinogram (ERG) are suitable methods to observe the function of ON- and OFF-pathways in vivo, respectively. It is clear that high intraocular pressure (IOP) might cause dysfunction of cone-dominated photopic negative response (PhNR) in monkeys with high IOP in ON-pathway. However, whether cone-dominated OFF-responses are also affected is less known. The aim of this study was to observe photopic OFF-responses of ERG in monkeys with high IOP. METHODS: Nine monkeys were involved in the experiment from January 2006 to December 2016. High IOP was induced in the right eye by laser coagulation of the mid-trabecular meshwork in five monkeys. Six years after the laser coagulation, both short- and long-flash of the photopic ERG were recorded. Stimulus light was red flashes superimposed on a blue background. Four normal monkeys were examined under the same ERG protocols as controls. Paired t- test was used to compare the difference of each ERG parameter between the lasered eye and the fellow eye. Analysis of variance (ANOVA) with Tukey adjustment was adopted to calculate the differences among the lasered eye, the fellow eye, and the eyes of normal monkeys. RESULTS: The mean amplitude of a-wave (11.73 ± 2.05) and PhNR (8.67 ± 2.44) in lasered eyes was significantly lower than that of a-wave (21.47 ± 3.15) and PhNR (22.05 ± 3.42) in fellow eyes (P = 0.03 and P = 0.01, respectively) in response to short flash. The mean amplitude of d-wave (1.60 ± 0.59) and i-wave (3.13 ± 0.64) was significantly reduced in the lasered eyes than that of d-wave (4.01 ± 0.56) and i-wave (8.79 ± 1.75) in the fellow eyes (P = 0.02 and P = 0.02, respectively) in response to long flash. CONCLUSIONS: Reduced OFF-responses are recorded in monkeys with high IOP when dysfunction of photoreceptor is involved. The reduced OFF-responses to long-flash stimulus show evidence of anomalous retinal circuitry in glaucomatous retinopathy.

The effects of different technologies on synthesis of CuInSe2 prepared by coreduction.

Solution thermal method was used to synthesize CuInSe2 powders from metal chlorides and SeO2 at 160~200°C. The phases of product samples were analyzed by x-ray diffraction (XRD), the size and morphology of the products were observed by JSM6380LA scanning electron microscope (SEM). The aim is to explore the best technology to obtain the pure CuInSe2 powders. Experimental results show that, CuInSe2 phase can be formed with metal chlorides by reacting for 20 h at 160°C, 180°C and 200°C and has XRD peaks corresponding to (112), (204) and (312) crystal planes, respectively. It consists of irregular spherical grains with about 0.2~0.5 µm in diameter, which agglomerate larger particles with average particle size about 1~3 µm. CuInSe2 phase was formed more easily at the temperature higher than 180°C and shows better crystallinity.

Dynein, kinesin and morphological changes in optic nerve axons in a rat model with cerebrospinal fluid pressure reduction: the Beijing Intracranial and Intraocular Pressure (iCOP) study.

PURPOSE: To examine the influence of experimentally reduced cerebrospinal fluid pressure (CSFP) as compared to elevated intraocular pressure (IOP) on axonal morphology and axonal motor proteins in retinal ganglion cells (RGCs). METHODS: The experimental study included 39 rats which underwent cerebrospinal fluid drainage for 6 hr, 30 rats which unilaterally underwent IOP elevation for 6 hr and 30 rats in a control group. Six hours after baseline, the animals were killed and the eyes were histologically and immunohistochemically examined. RESULTS: In experimental models in the high-IOP group and the low-CSFP group as compared to the control group, RGC axons became abnormally dilated and accumulated vesicles. Both groups as compared to the control group showed an accumulation of dynein IC (intermediate chain) at the optic nerve head and retina and a reduction in kinesin HC (heavy chain) immunoreactivity in the optic nerve fibre axons. As a corollary, Western blot analysis revealed an elevation of dynein IC protein levels in the optic nerve head and retina and a decrease in kinesin HC protein levels in the optic nerve. CONCLUSIONS: Experimental models with an acute IOP rise or with an acute CSFP reduction showed similar morphologic changes in the retinal ganglion cell axons and similar immunohistochemical changes in the axonal motor proteins kinesin HC and dynein IC. It supports the hypothesis that an experimental model with an acute reduction in CSFP as well as an experimental model with an acute rise in IOP may share similarities in the process of optic nerve damage.

Amperometric hydrogen peroxide and glucose biosensor based on NiFe2/ordered mesoporous carbon nanocomposites.

Nanocomposites of NiFex embedded in ordered mesoporous carbon (OMC) (x = 0, 1, 2) were prepared by a wet impregnation and hydrogen reduction process and were used to construct electrochemical biosensors for the amperometric detection of hydrogen peroxide (H2O2) or glucose. The NiFe2/OMC nanocomposites were demonstrated to have a large surface area, suitable mesoporous channels, many edge-plane-like defective sites, and a good distribution of alloyed nanoparticles. The NiFe2/OMC and Nafion modified glass carbon electrode (GCE) exhibited excellent electrocatalytic activities toward the reduction of H2O2 as well. By utilizing it as a bioplatform, GOx (glucose oxidase) cross-linked with Nafion was immobilized on the surface of the electrode for the construction of an amperometric glucose biosensor. Our results indicated that the amperometric hydrogen peroxide biosensor (NiFe2/OMC + Nafion + GCE) showed good analytical performances in term of a high sensitivity of 4.29 µA mM(-1) cm(-2), wide linearity from 6.2 to 42,710 µM and a low detection limit of 0.24 µM at a signal-to-noise ratio of 3 (S/N = 3). This biosensor exhibited excellent selectivity, high stability and negligible interference for the detection of H2O2. In addition, the immobilized enzyme on NiFe2/OMC + Nafion + GCE, retaining its bioactivity, exhibited a reversible two-proton and two-electron transfer reaction, a fast heterogeneous electron transfer rate and an effective Michaelis-Menten constant (K) (3.18 mM). The GOx + NiFe2/OMC + Nafion + GCE could be used to detect glucose based on the oxidation of glucose catalyzed by GOx and exhibited a wide detection range of 48.6-12,500 µM with a high sensitivity of 6.9 µA mM(-1) cm(-2) and a low detection limit of 2.7 µM (S/N = 3). The enzymic biosensor maintained a high selectivity and stability features, and shows great promise for application in the detection of glucose.

Safety evaluation of rabbit eyes on scleral collagen cross-linking by riboflavin and ultraviolet A.

BACKGROUND: To evaluate the safety of the scleral collagen cross-linking (CXL) transferred from corneal CXL in rabbit eyes using histology and electroretinography (ERG). METHODS: Stress-strain measurement was performed five rabbits 1 week after scleral CXL. Dark-adapted ERG was repeatedly applied on bilateral eyes of 10 rabbits before, and 1 week, 1 month and 3 months after the CXL operation. Histological analysis, terminal deoxynucleotidyl transferase dUTP nick-end labeling, the measurement of outer nuclear layer thickness and transmission electron microscopy were performed onto 15 rabbits at corresponding time points postoperatively. RESULTS: The mechanical and biochemical stability of rabbit scleral tissues was statistically increased after the scleral CXL (P = .00). However, the dark-adapted ERG amplitudes were statistically reduced 1 week, 1 month and 3 months postoperatively (P < 0.05). Compared with the control eyes, apoptotic cells and ultrastructural changes can be found in the retinal layers of scleral cross-linked eyes. CONCLUSIONS: According to the electrophysiological and histopathological results, the current scleral CXL laboratory technique is not safe enough for the postoperative visual function of rabbit eyes.

Long-term effect of laser-induced ocular hypertension on the cone electroretinogram and central macular thickness in monkeys.

OBJECTIVE: The purpose of this study was to investigate the long-term effect of laser-induced ocular hypertension on the cone electroretinogram (ERG) and retinal thickness in monkeys. BACKGROUND DATA: Degeneration of retinal nerve fiber layer (RNFL) and loss of retinal ganglion cells in the primate glaucoma model have been confirmed by histological studies and optical coherence tomography (OCT) images. However, it remains unclear whether the outer retina distal to the RGCs (e.g., photoreceptors) is involved in histological studies and in functional test. MATERIALS AND METHODS: Subjects were five monkeys with high intraocular pressure (IOP) induced in the right eye by laser. Six years after the laser coagulation of the mid-trabecular meshwork, RNFL, ganglion cell complex (GCC), central macular thickness (CMT), and the thickness of outer retinal layer (ORL) were measured by OCT. The photopic responses of ERG were recorded in response to red flashes on a blue background. The maximum cone amplitude (Rcone) and cone sensitivity (Scone) were calculated. RESULTS: Enlarged cup-to-disc (C/D) ratio was found in the lasered eyes. RNFL and GCC were significantly thinner in the lasered eyes (p<0.05), but no significant differences were found in CMT and the thickness of ORL compared with fellow eyes (p>0.05). Mean amplitude of the photopic negative response (PhNR), Mean Rcone were significantly lower in the lasered eye (p<0.05), and no significant differences of Scone were found between the two eyes (p>0.05). CONCLUSIONS: Long-term ocular hypertension induced by laser affects the function of cone photoreceptor in monkeys.

Optic neuropathy induced by experimentally reduced cerebrospinal fluid pressure in monkeys.

PURPOSE: To examine the influence of experimentally reduced cerebrospinal fluid pressure (CSFP) on retinal nerve fiber layer (RNFL) thickness and neuroretinal rim area of the optic nerve head. METHODS: This experimental study included nine monkeys that underwent implantation of a lumbar-peritoneal cerebrospinal fluid (CSF) shunt. In the study group (n = 4 monkeys), the shunt was opened to achieve a CSF of approximately 40 mm H2O, while the shunt remained closed in the control group (n = 5 monkeys). At baseline and in monthly intervals thereafter, optical coherence tomographic and photographic images of the optic nerve head and RNFL were taken of all monkeys. RESULTS: Two out of four monkeys in the study group showed bilaterally a progressive reduction in RNFL thickness between 12% and 30%, reduction in neuroretinal rim area and volume, and increase in cup-to-disc area ratios. A third monkey developed a splinter-like disc hemorrhage in one eye. The fourth monkey in the study group did not develop morphologic changes during follow-up, nor did any monkey in the control group. CONCLUSIONS: Experimental and chronic reduction in CSF in monkeys was associated with the development of an optic neuropathy in some monkeys.

Reproducibility of macular, retinal nerve fiber layer, and ONH measurements by OCT in Rhesus monkeys: The Beijing Intracranial and Intraocular Pressure (iCOP) Study.

PURPOSE: We evaluated repeatability and reproducibility of measurements of the retinal nerve fiber layer thickness (RNFLT), optic nerve head (ONH), and macular inner retinal layer (MIRL) by RTVue spectral-domain optical coherence tomography (OCT) in normal Rhesus monkeys. METHODS: The experimental study included 15 adult Rhesus macaque monkeys. RNFLT, ONH parameters (area of disc, cup, and rim; volume of cup and rim; and cup-to-disc ratios), and MIRL thickness were imaged at three separate examinations within one month. Each eye was imaged three times at the first examination, and once at each of the two following examinations. We determined the intra-session and inter-session (inter-visit) within-subject SD (Sw), precision (1.96 × Sw), coefficient of variation (CVw, 100 × Sw/overall mean), and intraclass correlation coefficient (ICC). RESULTS: For the intra-session repeatability, ICC values ranged between 0.97 and 1.00 for all ONH parameters, and between 0.80 and 0.98 for all regional RNFLT parameters, with a value of 0.97 for the average RNFLT. For the inter-session (inter-visit) reproducibility, ICC values ranged from 0.93-1.00 for the ONH measurements and from 0.63-0.97 for regional RNFLT parameters, with a value of 0.96 for the average RNFLT. Again, the ICC values were lowest in the temporal inferior and temporal superior regions. The ICC value for the average MIRL thickness was 0.95. CONCLUSIONS: Repeatability and reproducibility of spectral-domain OCT measurements of the RNFL, ONH, and MIRL were high in normal monkey eyes. Spectral-domain OCT may be suitable to assess changes in follow-up examinations of monkeys with experimental glaucoma.

Long-term rescue of rat retinal ganglion cells and visual function by AAV-mediated BDNF expression after acute elevation of intraocular pressure.

PURPOSE: To evaluate the ability of increased expression of brain-derived neurotrophic factor (BDNF) using adenoassociated viral (AAV) vector to prevent the loss of rat retinal ganglion cells (RGCs) and visual function after acute elevation of intraocular pressure (IOP). METHODS: AAV vectors (expressing BDNF or GFP) were injected into the vitreous 6 hours after a transient IOP elevation to 130 mm Hg for 45 minutes. Protective effects were evaluated by counting RGCs retrogradely labeled with fluorogold (FG) from the superior colliculus, measuring the amplitude and the latency of the P1 component of the visual evoked potential (VEP), and observing the visual acuity and contrast sensitivity in awake and behaving animals. RESULTS: RGC numbers decreased continuously to 9 weeks after the elevation of IOP. FG-positive RGC loss was significantly decreased in the retinas treated with AAV-BDNF at 3, 6, and 9 weeks after the insult, with corresponding improvements in VEP parameters. Supplementing BDNF protein once to compensate for the slow onset of AAV-mediated gene expression rescued a larger number of RGCs and the parameters of the VEP. Visual acuity and contrast sensitivity were significantly improved in all treated groups, with the largest improvement in the combined-therapy group, and were maintained for up to 70 weeks. The authors further demonstrated that BDNF rescued the RGCs by activating TrkB receptors through both autocrine and paracrine mechanisms. CONCLUSIONS: AAV-mediated BDNF expression in the rat retina achieved a sustained rescue of RGCs and visual function after an acute elevation of IOP.

Suprachoroidal injection of ketorolac tromethamine does not cause retinal damage.

Rabbit right eyes were injected with 3 or 6 mg ketorolac tromethamine into the suprachoroidal space. Electroretinography results demonstrated no abnormal changes in rod cell response, maximum rod cell or cone cell mixing reaction, oscillation potential, cone cell response, waveform, amplitude, and potential of 30 Hz scintillation response in right eyes before injection, and at 1, 2, and 4 weeks after injection. There was no difference between left (control) and right eyes. Under light microscopy, the histomorphology of cells in each retinal layer was normal at 4 weeks following 6 mg ketorolac tromethamine administration. These results indicate that a single suprachoroidal injection of 3 or 6 mg ketorolac tromethamine into rabbits was safe. Suprachoroidal space injection appears to be safe.

The role of CCR1 expression in the retinal degeneration in rd mice.

PURPOSE: Chemokine receptors are reported to be involved in neuronal cell death and CNS neurodegenerative diseases. The aim of the current study was to investigate the expression of CCR1, a major chemokine receptor for CC chemokines in retinal dystrophy in rd (retinal degeneration) mice and further explore its role in photoreceptor degeneration. MATERIALS AND METHODS: The expression levels of CCR1 mRNA in the whole control and rd retinas at postnatal days (P) 8, 10, 12, 14, 16, and 18 were determined by RT-PCR assay. Location of CCR1 in the retina of rd mice at each age group was studied by immunohistochemical analysis. Expression of CCR1 in the photoreceptor cells and apoptotic cells was determined by double labeling. RESULTS: Expression of CCR1 mRNA was noted in both control and rd retinas at each age group. CCR1-positive cells started to emerge in the outer nuclear layer (ONL) in rd retinas at P8 and reached a peak at P12 and P14. Double labeling of CCR1 with rhodopsin, CD11b, or TUNEL staining showed expression of CCR1 in the photoreceptor cells, rather than in the microglial cells. Partial CCR1 expression was observed in some of the apoptotic photoreceptor cells. CONCLUSIONS: Expression of CCR1 in the photoreceptor cells was increased with the progress of retinal degeneration in rd mice. Activation of CCR1 may play a role in the photoreceptor apoptosis.

Penetrability of interleukin-1beta and its effect on the concentration of tumor necrosis factor-alpha and interleukin-6 in the aqueous humor of rabbits treated with interleukin-1beta.

BACKGROUND: Interleukin (IL)-1beta may effectively decrease introcular pressure (IOP) when administered by subconjunctival injection in normal rabbit. However, IL-1beta is a large molecular agent and an inflammation factor. The aim of this study was to evaluate the penetrability of IL-1beta, and the concentrations of both tumor necrosis factor (TNF)-alpha and IL-6 in the aqueous humor of normal rabbits treated with IL-1beta. METHODS: A total of 170 rabbits were used in the study and were assigned to several different treatment groups as follows: 125 of the rabbits were assigned to two groups. In one group, 33 rabbits were injected subconjunctivally with IL-1beta and 39 were injected with saline alone. In the other group, 27 rabbits were given eye drops containing IL-1beta (400 ng/ml) and 26 were given saline alone. Aqueous humor (AH) was drawn and the concentration of IL-1beta within the fluid measured. The IOP was measured in another six rabbits after administration of eye drops containing IL-1beta (400 ng/ml). A further 20 rabbits were assigned to 3 groups as follows: eight untreated normal controls; six injected subconjunctivally with IL-1beta; and six injected subconjunctivally with saline alone. AH was drawn and the concentration of TNF-alpha in the fluid was measured. Another 19 rabbits were assigned to 3 groups as follows: seven untreated normal controls; and six injected subconjunctivally with IL-1beta; and six injected subconjunctivally with saline alone. AH was drawn and the concentration of IL-6 in the fluid measured. Measurement of cytokine concentration was by radio-immunoassay in all cases. RESULTS: The IL-1beta concentration in the AH was higher in those animals in which it had been administered subconjunctivally (P < 0.01). The IL-1beta concentration in the AH of the animals given eye drops was almost the same as that in the controls (P > 0.05). The administration of IL-1beta in the form of eye drops had little effect upon IOP reduction. Lower TNF-alpha concentrations were seen in the AH after the subconjunctival administration of IL-1beta, but the concentration of IL-6 was the same as in the normal controls. CONCLUSIONS: IL-1beta shows good corneal penetrability after subconjunctival injection into normal rabbit eyes. The IOP reduction induced by IL-1beta is unlikely be associated with an inflammatory response.

Development of the electroretinographic oscillatory potentials in normal and ROP rats.

PURPOSE: To study the development of the electroretinographic (ERG) oscillatory potentials (OPs) in rats and to compare normal OPs with those in a rat model of retinopathy of prematurity (ROP). METHODS: Following a longitudinal design, ERG responses to a greater than 5 log unit range of full-field stimuli were recorded in dark-adapted rats at postnatal day (P) 18, P31, P47, and P67. The ERG records were digitally filtered (60-235 Hz), and the trough-to-peak amplitudes and implicit times of OP2, OP3, OP4, and OP5 were measured. Additionally, rats with oxygen-induced retinopathy, a model of ROP, were studied at P31. RESULTS: Generally, OP amplitude increased and implicit time decreased with increasing stimulus intensity. The shape of the stimulus-response functions changed with age. The amplitudes of OP2, OP3, and OP4 were largest at P31. OP5 was largest at P47. All OPs were significantly affected in ROP rats; OP5 was least affected by ROP. CONCLUSIONS: A prolonged normal course of OP development, which featured waxing and waning of amplitudes, was observed and might have been consequent to maturation and then to final refinements of inner retinal circuitry. In ROP rats, marked attenuation of early OPs was consistent with persistent dysfunction of photoreceptors, and significant attenuation of the late OP5 was evidence of compromised function of inner retinal circuitry.

The retinal vasculature and function of the neural retina in a rat model of retinopathy of prematurity.

PURPOSE: In a rat model of retinopathy of prematurity (ROP), the retinal vasculature and function of the neural retina were studied longitudinally. Vascular and neural parameters were evaluated for significant relationships. METHODS: Retinopathy was induced by exposing newborn rats to alternating 50% and 10% oxygen until age 14 days. To evaluate the function of the neural retina, electroretinographic (ERG) responses to full-field stimuli were recorded from dark-adapted rats at ages 18 and 31 days. Sensitivity and saturated amplitude of photoreceptor and postreceptor activity were derived from ERG a- and b- waves. To evaluate the retinal vasculature, digital fundus photographs were obtained at the same ages, and the tortuosity indices of the arterioles (TIA) and venules (TIV) were calculated. ROP rats and room-air-raised control animals were compared. Vascular and response parameters were evaluated for significant relationships. RESULTS: In ROP rats, TIA was high at 18 days and decreased in every rat to nearly normal levels by 31 days. TIV was less affected by ROP or age. Deficits in all receptor and post-receptor response parameters were present in 18-day-old ROP rats. Post-receptor sensitivity recovered completely by 31 days. Deficits in other response parameters persisted. No significant correlations between vascular and ERG parameters were found in 18-day-old ROP rats. CONCLUSIONS: Noninvasive, longitudinal measures in this model of ROP showed significant abnormalities in both the retinal vasculature and function of the neural retina that were most marked at age 18 days. However, vascular and neural abnormalities did not correlate.