Normal Retinal Function Research Articles

A Novel Role for the Immunoproteasome in Retinal Function

The immunoproteasome is a proteasome subtype with a well-characterized role in the immune system. The presence of high immunoproteasome concentrations in the photoreceptors and synaptic regions of the immune-privileged retina implies a role in visual transmission. In this study, immunoproteasome knockout (KO) mice lacking either one (lmp7(-/-), L7) or two (lmp7(-/-)/mecl-1(-/-), L7M1) catalytic subunits of the immunoproteasome were used to test the hypothesis that it is essential for the maintenance of normal retinal function. Wild-type (WT) and immunoproteasome KO mice lacking either one (L7) or two (L7M1) catalytic subunits of the immunoproteasome were studied to determine the importance of the immunoproteasome in maintaining normal retinal function and morphology. Changes in retinal morphology were assessed in mice 2 to 24 months of age. Retinal function was measured with electroretinography (ERG), and relative content of select retinal proteins was assessed by immunoblot analysis. Retinal morphometry showed no major abnormalities in age-matched WT or KO mice. No significant difference was observed in the levels of proteins involved in vision transmission. ERGs from KO mice exhibited an approximate 25% decrease in amplitude of the dark- and light-adapted b-waves and faster dark-adapted b-wave implicit times. Immunoproteasome deficiency causes defects in bipolar cell response. These results support a previously unrecognized role for the immunoproteasome in vision transmission.

Sac-0601 prevents retinal vascular leakage in a mouse model of diabetic retinopathy

Endothelium integrity is important for the normal functioning of vessels, the disruption of which can lead to disease. The blood-retinal barrier required for normal retinal function is compromised in diabetic retinopathy, causing retinal vascular leakage. Previously, we demonstrated the ability of Sac-0601[((2R,3S)-3-acetoxy-6-((3S,10R,13R,17R)-10,13-dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yloxy)-3,6-dihydro-2H-pyran-2-yl)methyl acetate], a pseudo-sugar derivative of cholesterol, to increase survival of retinal endothelial cells. In the present study, we evaluated the ability of Sac-0601 to prevent retinal vascular leakages in vitro and in vivo. Sac-0601 treatment blocked VEGF-induced formation of actin stress fibers and stabilized the cortical actin ring in retinal endothelial cells. It also inhibited degradation of occludin, an important tight junction protein, and blocked VEGF-induced disruption of its linear pattern at the cell border. The [ 14C] sucrose permeability assay demonstrated that Sac-0601 was able to prevent VEGF-induced retinal endothelial permeability. The compound inhibited the vascular leakage in retina of mice intravitreally injected with VEGF. And it also significantly reduced the leakage in retina of diabetic retinopathy mice model. Taken together, our findings suggest the potential therapeutic usefulness of Sac-0601 for retinal vascular permeability diseases.

The effect of descemet-stripping automated endothelial keratoplasty combined with phacoemulsification cataract surgery or lens exchange

To evaluate the effect and explore the complications of Descemet-stripping automated endothelial keratoplasty (DSAEK) combined with phacoemulsification cataract surgery or lens exchange in corneal endothelial dysfunction eyes with lens disorders. Retrospective case series. Eighteen consecutive cases (20 eyes) were performed DSAEK combined with lens surgery from December 2007 to December 2008 in Department of Ophthalmology, Peking University Third Hospital. Five cases (7 eyes) were performed DSAEK combined with phacoemulsification and intraocular lens (IOL) insertion. Seven cases were combined with anterior chamber IOL extraction, anterior vitrectomy and posterior chamber IOL insertion. Six aphakia cases were performed with DSAEK combined with anterior vitrectomy and sclera fixation posterior chamber IOL insertion. Postoperatively, the visual acuity, corneal transparency, central corneal thickness (CCT), endothelial cell density (ECD) and complications were observed during the follow-up. The irritation was disappeared in all of patients. All of the corneas became transparent. The preoperative and postoperative mean CCT of the recipient beds was 859 µm and 553 µm respectively. T value was 5.303 (t = 5.303, P < 0.01). It was extremely significant difference. The mean ECD of the donors was 2987 cells/mm(2). The ECD was 1803 cells/mm(2) in three months postoperatively. The rate of endothelial cells loss was 41%. The visual acuity improved significantly except 9 eyes which had fundus disorders. Six eyes were better than 0.8. It was 55% in normal retinal function patients (6/11). The inflammatory reaction of the anterior chamber IOL eyes was most serious. Six eyes underwent graft dislocation. Five cases underwent high intraocular pressure. One case occurred graft rejection. These complications occurred in anterior chamber IOL eyes. DSAEK combined with phacoemulsification cataract surgery or lens exchange is a safe and effective surgical treatment for corneal endothelial dysfunction with lens disorders. More complications occur in anterior chamber IOL eyes. DSAEK should be cautiously chosen in abnormal iris and chamber angle structural eyes.

The ins and outs of cholesterol in the vertebrate retina

The vertebrate retina has multiple demands for utilization of cholesterol and must meet those demands either by synthesizing its own supply of cholesterol or by importing cholesterol from extraretinal sources, or both. Unlike the blood-brain barrier, the blood-retina barrier allows uptake of cholesterol from the circulation via a lipoprotein-based/receptor-mediated mechanism. Under normal conditions, cholesterol homeostasis is tightly regulated; also, cholesterol exists in the neural retina overwhelmingly in unesterified form, and sterol intermediates are present in minimal to negligible quantities. However, under certain pathological conditions, either due to an inborn error in cholesterol biosynthesis or as a consequence of exposure to selective inhibitors of enzymes in the cholesterol pathway, the ratio of sterol intermediates to cholesterol in the retina can rise dramatically and persist, in some cases resulting in progressive degeneration that significantly compromises the structure and function of the retina. Although the relative contributions of de novo synthesis versus extraretinal uptake are not yet known, herein we review what is known about these processes and the dynamics of cholesterol in the vertebrate retina and indicate some future avenues of research in this area.

PARP1 Gene Knock-Out Increases Resistance to Retinal Degeneration without Affecting Retinal Function

Retinitis pigmentosa (RP) is a group of inherited neurodegenerative diseases affecting photoreceptors and causing blindness in humans. Previously, excessive activation of enzymes belonging to the poly-ADP-ribose polymerase (PARP) group was shown to be involved in photoreceptor degeneration in the human homologous rd1 mouse model for RP. Since there are at least 16 different PARP isoforms, we investigated the exact relevance of the predominant isoform - PARP1 - for photoreceptor cell death using PARP1 knock-out (KO) mice. In vivo and ex vivo morphological analysis using optic coherence tomography (OCT) and conventional histology revealed no major alterations of retinal phenotype when compared to wild-type (wt). Likewise, retinal function as assessed by electroretinography (ERG) was normal in PARP1 KO animals. We then used retinal explant cultures derived from wt, rd1, and PARP1 KO animals to test their susceptibility to chemically induced photoreceptor degeneration. Since photoreceptor degeneration in the rd1 retina is triggered by a loss-of-function in phosphodiesterase-6 (PDE6), we used selective PDE6 inhibition to emulate the rd1 situation on non-rd1 genotypes. While wt retina subjected to PDE6 inhibition showed massive photoreceptor degeneration comparable to rd1 retina, in the PARP1 KO situation, cell death was robustly reduced. Together, these findings demonstrate that PARP1 activity is in principle dispensable for normal retinal function, but is of major importance for photoreceptor degeneration under pathological conditions. Moreover, our results suggest that PARP dependent cell death or PARthanatos may play a major role in retinal degeneration and highlight the possibility to use specific PARP inhibitors for the treatment of RP.

Long-chain and very long-chain polyunsaturated fatty acids in ocular aging and age-related macular degeneration

Retinal long-chain PUFAs (LC-PUFAs, C(12)-C(22)) play important roles in normal human retinal function and visual development, and some epidemiological studies of LC-PUFA intake suggest a protective role against the incidence of advanced age-related macular degeneration (AMD). On the other hand, retinal very long-chain PUFAs (VLC-PUFAs, C(n>22)) have received much less attention since their identification decades ago, due to their minor abundance and more difficult assays, but recent discoveries that defects in VLC-PUFA synthetic enzymes are associated with rare forms of inherited macular degenerations have refocused attention on their potential roles in retinal health and disease. We thus developed improved GC-MS methods to detect LC-PUFAs and VLC-PUFAs, and we then applied them to the study of their changes in ocular aging and AMD. With ocular aging, some VLC-PUFAs in retina and retinal pigment epithelium (RPE)/choroid peaked in middle age. Compared with age-matched normal donors, docosahexaenoic acid, adrenic acid, and some VLC-PUFAs in AMD retina and RPE/choroid were significantly decreased, whereas the ratio of n-6/n-3 PUFAs was significantly increased. All these findings suggest that deficiency of LC-PUFAs and VLC-PUFAs, and/or an imbalance of n-6/n-3 PUFAs, may be involved in AMD pathology.

Bim is responsible for the inherent sensitivity of the developing retinal vasculature to hyperoxia

Apoptosis plays an important role in development and remodeling of vasculature during organogenesis. Coordinated branching and remodeling of the retinal vascular tree is essential for normal retinal function. Bcl-2 family members, such as bim not only influence apoptosis, but also cell adhesive and migratory properties essential during vascular development. Here we examined the impact of bim deficiency on postnatal retinal vascularization, as well as retinal neovascularization during oxygen-induced ischemic retinopathy (OIR) and laser-induced choroidal neovascularization. Loss of bim expression was associated with increased retinal vascular density in mature animals. This was mainly attributed to increased numbers of pericytes and endothelial cells. However, the initial spread of the superficial layer of retinal vasculature and, the appearance and density of the tip cells were similar in bim+/+ and bim−/− mice. In addition, hyaloid vessel regression was attenuated in the absence of bim. Furthermore, in the absence of bim retinal vessel obliteration and neovascularization did not occur during OIR. Instead, normal inner retinal vascularization proceeded independent of changes in oxygen levels. In contrast, choroidal neovascularization occurred equally well in bim+/+ and bim−/− mice. Together our data suggest bim expression may be responsible for the inherent sensitivity of the developing retinal vasculature to changes in oxygen levels, and promotes vessel obliteration in response to hyperoxia.

Padronização do eletrorretinograma de campo total em cães

Eletrorretinograma (ERG) é o meio diagnóstico objetivo e não-invasivo para avaliar a função retiniana e detectar precocemente, em várias espécies, lesões nas suas camadas mais externas. As indicações mais comuns para ERG em cães são: avaliação pré-cirúrgica de pacientes com catarata, caracterização de distúrbios que causam cegueira, além de servir como importante modelo para o estudo da distrofia retiniana que acomete o homem. Vários são os fatores que podem alterar o ERG tais como: eletrorretinógrafo, fonte de estimulação luminosa, tipo do eletrodo, tempo de adaptação ao escuro, tamanho pupilar, opacidade de meios e protocolo de sedação ou anestesia; além da espécie, raça e idade. Objetivou-se com este estudo padronizar o ERG para cães submetidos à sedação, seguindo o protocolo da International Society for Clinical Electrophysiology of Vision (ISCEV), utilizando Ganzfeld e eletrodos Burian Allen. Foram realizados 233 eletrorretinogramas em cães, 147 fêmeas e 86 machos, com idades entre um e 14 anos. Dos 233 cães examinados, 100 apresentavam catarata em diferentes estágios de maturação, 72 eram diabéticos e apresentavam catarata madura ou hipermadura, 26 apresentaram eletrorretinograma compatível com degeneração retiniana progressiva, três apresentaram eletrorretinograma compatível com síndrome da degeneração retiniana adquirida subitamente e 32 não apresentaram lesão retiniana capaz de atenuar as respostas do ERG, sendo considerados normais quanto à função retiniana. A sedação foi capaz de produzir boa imobilização do paciente sem rotacionar o bulbo ocular, permitindo adequada estimulação retiniana bilateralmente, com auxílio do Ganzfeld. O sistema eletrodiagnóstico Veris registrou com sucesso e simultaneamente de ambos os olhos, as cinco respostas preconizadas pela ISCEV. Como o ERG de campo total tornou-se exame fundamental na rotina oftalmológica, sua padronização é indispensável quando se objetiva comparar resultados de laboratórios distintos. A confiabilidade e reprodutibilidade deste protocolo foi demonstrada com a obtenção de registros de ótima qualidade utilizando protocolo padrão da ISCEV, eletrorretinógrafo Veris, Ganzfeld e eletrodos Burian Allen nos cães submetidos à sedação.

The regulation of retinal blood flow in the healthy and diseased eye

AbstractThe maintenance of normal retinal structure and function depends on a tightly regulated environment. This requires intact blood‐retinal barriers as well as an efficient regulation of blood flow and delivery of oxygen and metabolic substrates to the retinal tissue. Thanks to the development of noninvasive techniques allowing the quantitative assessment of retinal hemodynamics in the human eye, much progress has been achieved in recent years in the understanding of retinal blood flow regulation and the mechanisms involved in this physiological process. Retinal blood flow is regulated by the interaction of myogenic and metabolic mechanisms through the release of vasoactive substances by the vascular endothelium and retinal tissue surrounding the arteriolar wall. This regulation is achieved by adaptation of the vascular tone of the resistance vessels to changes in the perfusion pressure or metabolic needs of the tissue. This adaptation occurs through the interaction of multiple mechanisms affecting mainly the arteriolar smooth muscle cells. These mechanisms, which involve the close interaction between nitric oxide, lactate and arachidonic acid metabolites released by the neuronal and glial cells, optimize blood flow according to the metabolic needs of the tissue. Impairments of structure and function of the retinal neural tissue and endothelium during the evolution of ischemic microangiopathies affect the interaction of the retinal metabolic pathways and alter blood flow regulation. Assessing retinal blood flow and its response to various physiological stimuli and the mechanisms mediating and modulating these responses has provided important insight into these pathological processes, which lead to severe losses of vision.

Loss of chromatic sensitivity in AMD and diabetes: a comparative study

Abnormalities in rod and cone photoreceptor morphology have been reported in normal aging retinas in the absence of known pathology and have been taken as an indicator of susceptibility to retinal disease. Some loss of visual performance may therefore precede retinal structural changes that can be detected reliably using conventional fundus imaging techniques. Red/green (RG) and yellow/blue (YB) colour discrimination thresholds are sensitive measures of normal retinal function and poor YB discrimination is often taken as an indicator of retinal disease, though it is generally acknowledged that RG loss is also present in most cases of acquired deficiency. Although structural changes in age-related macular degeneration (AMD) and diabetes share some similarities, significant differences remain and this may result in different patterns of RG and YB loss. The aim of this study was to quantify and compare the severity of RG and YB loss of chromatic sensitivity in patients with AMD and diabetes. Patients with varying severity of AMD and diabetes and normal subjects of similar age were recruited for the study. RG and YB colour detection thresholds were measured in the two groups of patients and the control group, using the Colour Assessment and Diagnosis (CAD) test. Each AMD subject investigated showed significant, but unequal loss of YB and RG chromatic sensitivity, with YB discrimination showing the greatest loss. Diabetic subjects also exhibited reduced chromatic sensitivity, but with almost equal and highly correlated RG and YB thresholds (R(2) = 0.99). The severity of colour vision loss measured with the CAD test also correlates well with a clinical classification index of disease progression in AMD, and with the level of hyperglycaemic control in diabetes. These findings suggest that accurate measurements of RG and YB colour thresholds can provide a sensitive measure of functional change in diseases of the retina with patterns of loss that differ significantly in AMD and diabetes.

Current researches on effects of retinal Muller cell on glaucomatous retinal ganglion cells

Retinal ganglion cells （RGCs） apoptosis is the pathologic characteristic of glaucoma.Retinal Muller cells is a predominant glial element.It plays an important role in maintaining normal retinal structure and function,including supporting neurons,maintaining homeostasis of retinal extracellular milieu and modulating neuron activity,etc.In recent years,glaucoma has been found to be associated with a reactive retinal Muller cells changes,which may involve in neuronal apoptosis and meanwhile support the survival of retinal neurons.The progress in the study of the mechanism of Muller cells participating in the glaucomatous neuronal apoptosis and survival was reviewed. Key words: Muller cells; glaucoma; retinal ganglion cells; apoptosis

Retinal very long-chain PUFAs: new insights from studies on ELOVL4 protein

Compared with other mammalian tissues, retina is highly enriched in PUFA. Long-chain PUFA (LC-PUFA; C18-C24) are essential FAs that are enriched in the retina and are necessary for maintenance of normal retinal development and function. The retina, brain, and sperm also contain very LC-PUFA (VLC-PUFA; >C24). Although VLC-PUFA were discovered more than two decades ago, very little is known about their biosynthesis and functional roles in the retina. This is due mainly to intrinsic difficulties associated with working on these unusually long polyunsaturated hydrocarbon chains and their existence in small amounts. Recent studies on the FA elongase elongation of very long chain fatty acids-4 (ELOVL4) protein, however, suggest that VLC-PUFA probably play some uniquely important roles in the retina as well as the other tissues. Mutations in the ELOVL4 gene are found in patients with autosomal dominant Stargardt disease. Here, we review the recent literature on VLC-PUFA with special emphasis on the elongases responsible for their synthesis. We focus on a novel elongase, ELOVL4, involved in the synthesis of VLC-PUFA, and the importance of these FAs in maintaining the structural and functional integrity of retinal photoreceptors.

Knockdown of FABP5 mRNA decreases cellular cholesterol levels and results in decreased apoB100 secretion and triglyceride accumulation in ARPE-19 cells

To maintain normal retinal function, retinal pigment epithelial (RPE) cells engulf photoreceptor outer segments (ROS) enriched in free fatty acids (FFAs). We have previously demonstrated fatty acid-binding protein 5 (FABP5) downregulation in the RPE/choroidal complex in a mouse model of aging and early age-related macular degeneration. FABPs are involved in intracellular transport of FFAs and their targeting to specific metabolic pathways. To elucidate the role of FABP5 in lipid metabolism, the production of the FABP5 protein in a human RPE cell line was inhibited using RNA interference technology. As a result, the levels of cholesterol and cholesterol ester were decreased by about 40%, whereas FFAs and triglycerides were increased by 18 and 67% after siRNA treatment, respectively. Some species of phospholipids were decreased in siRNA-treated cells. Cellular lipid droplets were evident and apoB secretion was decreased by 76% in these cells. Additionally, we discovered that ARPE-19 cells could synthesize and secrete Apolipoprotein B100 (apoB100), which may serve as a backbone structure for the formation of lipoprotein particles in these cells. Our results indicate that FABP5 mRNA knockdown results in the accumulation of cellular triglycerides, decreased cholesterol levels, and reduced secretion of apoB100 protein and lipoprotein-like particles. These observations indicated that FABP5 plays a critical role in lipid metabolism in RPE cells, suggesting that FABP5 downregulation in the RPE/choroid complex in vivo might contribute to aging and early age-related macular degeneration.

Disseminated mast cell tumor infiltrating the sphenoid bone and causing blindness in a dog

Mast cell tumors are found in most organs and tissues with variable biologic behavior in dogs. This case illustrates the clinical and magnetic resonance imaging (MRI) findings in a dog with disseminated mast cell tumor infiltrating the sphenoid bones. A 6-year-old male neutered Greyhound presented with a 3-day history of acute onset of blindness. General physical examination was normal. Neurological examination revealed mildly disorientated mental status, absent menace response in both eyes, bilaterally decreased vestibulo-oculocephalic reflexes and absent direct and consensual pupillary light reflex in both eyes. An electroretinogram indicated normal retinal function in both eyes. A lesion involving the middle and rostral cranial fossa was suspected. Hematology and serum biochemistry were normal except decreased urea (1.2 mmol/L). MRI of the head revealed heterogeneous signal intensity of the sphenoid bones on T2-weighted images and loss of their normal internal architecture. Cerebrospinal fluid analysis was normal. Abdominal ultrasound revealed hepatosplenomegaly and mesenteric lymphadenopathy. Fine needle aspirates were taken from the jejunal lymph nodes and the spleen. Results were consistent with disseminated mast cell tumor. The owner declined any treatment and the dog was euthanatized. Postmortem examination confirmed disseminated mast cell tumor affecting multiple organs, including the sphenoid bones. To our knowledge, this is the first case describing MRI features of disseminated mast cell tumor affecting the sphenoid bones and causing acute onset of blindness in a dog.

Autofluorescence Imaging in Rubella Retinopathy

Purpose: To demonstrate that fundus autofluorescence (FAF) imaging aides the diagnosis of rubella retinopathy (RR). Methods: Four patients with sensorineural hearing loss underwent ophthalmic exams, electro-retinogram testing (ERG), and FAF in both eyes. Fluorescein angiogram (FA) was performed in one case. Results: Salt-and-pepper retinopathy was observed in seven eyes. FAF highlighted the fundus abnormalities with stippled fluorescence in all seven eyes. ERG showed normal retinal function in all eyes. Choroidal neovascularization was identified by FA in one eye. Conclusions: FAF is sensitive to the retinal pigment epithelium disturbance caused by rubella and noninvasively helps establish the diagnosis of RR.

Lack of Niemann–Pick type C1 induces age-related degeneration in the mouse retina

Niemann–Pick type C (NPC) disease is an inherited lysosomal storage disease and caused by mutations in Npc1 or Npc2, which mediate cooperatively the egress of cholesterol from lysosomes. The disease entails progressive neurodegeneration, whose cause is poorly understood. Here, we report that Npc1 is distributed in distinct layers of the mouse retina and that its deficiency causes striking retinal degeneration in 2-month-old mice with signs of age-related maculopathies. This includes impaired visual function, accumulation of lipofuscin in the retinal pigment epithelium layer, degeneration of photoreceptor outer segments, disruption of synaptic layers and an increase in autophagy markers in the ganglion cell layer. Moreover, the lack of Npc1 results in the upregulation of proteins that mediate cellular cholesterol release in the retina. Our findings suggest that Npc1 is required for normal retinal function and that its absence may serve as model to study age-related degeneration of the retina.

Normal Central Retinal Function and Structure Preserved in Retinitis Pigmentosa

To determine whether normal function and structure, as recently found in forms of Usher syndrome, also occur in a population of patients with nonsyndromic retinitis pigmentosa (RP). Patients with simplex, multiplex, or autosomal recessive RP (n = 238; ages 9-82 years) were studied with static chromatic perimetry. A subset was evaluated with optical coherence tomography (OCT). Co-localized visual sensitivity and photoreceptor nuclear layer thickness were measured across the central retina to establish the relationship of function and structure. Comparisons were made to patients with Usher syndrome (n = 83, ages 10-69 years). Cross-sectional psychophysical data identified patients with RP who had normal rod- and cone-mediated function in the central retina. There were two other patterns with greater dysfunction, and longitudinal data confirmed that progression can occur from normal rod and cone function to cone-only central islands. The retinal extent of normal laminar architecture by OCT corresponded to the extent of normal visual function in patients with RP. Central retinal preservation of normal function and structure did not show a relationship with age or retained peripheral function. Usher syndrome results were like those in nonsyndromic RP. Regional disease variation is a well-known finding in RP. Unexpected was the observation that patients with presumed recessive RP can have regions with functionally and structurally normal retina. Such patients will require special consideration in future clinical trials of either focal or systemic treatment. Whether there is a common molecular mechanism shared by forms of RP with normal regions of retina warrants further study.

Cellular signaling and factors involved in Müller cell gliosis: Neuroprotective and detrimental effects

Müller cells are active players in normal retinal function and in virtually all forms of retinal injury and disease. Reactive Müller cells protect the tissue from further damage and preserve tissue function by the release of antioxidants and neurotrophic factors, and may contribute to retinal regeneration by the generation of neural progenitor/stem cells. However, Müller cell gliosis can also contribute to neurodegeneration and impedes regenerative processes in the retinal tissue by the formation of glial scars. This article provides an overview of the neuroprotective and detrimental effects of Müller cell gliosis, with accounts on the cellular signal transduction mechanisms and factors which are implicated in Müller cell-mediated neuroprotection, immunomodulation, regulation of Müller cell proliferation, upregulation of intermediate filaments, glial scar formation, and the generation of neural progenitor/stem cells. A proper understanding of the signaling mechanisms implicated in gliotic alterations of Müller cells is essential for the development of efficient therapeutic strategies that increase the supportive/protective and decrease the destructive roles of gliosis.

Influence of microglia on retinal progenitor cell turnover and cell replacement

Microglia within the retina are continually replaced from the bone marrow and are the resident myeloid-derived cells within the retina. Throughout life, microglial function is conditioned by the microenvironment affording immunomodulation to control inflammation as well as functioning to enable normal development and, during adulthood, maintain normal retinal function. In adulthood, recent evidence supports the concept that the retina continues to replace cells to maintain optimal function. Although in some cases after injury, degeneration, or inflammation there remains an inextricable decline in visual function inferring a deficit in cell replacement, the deficit could be explained by microglial cell activation influencing the ability of either retinal progenitor cells or recruited progenitor cells to integrate and differentiate appropriately. Myeloid cell response differs depending on insult: it is evident that during inflammation microglia and the infiltrating myeloid cell function are conditioned by the cytokine environment. Indeed, modulating myeloid cell function therapeutically suppresses disease in experimental models of autoimmunity, whereas in non-inflammatory models microglia have little or no effect on the course of degeneration. The extent of myeloid activation can help determine retinal progenitor cell turnover. Retinal progenitor cells may be isolated from adult human retina, which, albeit limited, display mitotic activity and can differentiate. Microglial activation secreting IL-6 limits progenitor cell turnover and the extent to which differentiation to post-mitotic retinal cells occurs. Such experimental data illustrate the need to develop methods to replenish normal retinal myeloid cell function facilitating integration, either by cell transplantation or by encouraging retinal progenitor cells to recover retinal function.

Mathematical Modelling of Intraretinal Oxygen Partial Pressure

Purpose: The aim of our present work is to develop a simple steady state model for intraretinal oxygen partial pressure distribution and to investigate the effect of various model parameters on the partial pressure distribution under adapted conditions of light and darkness.. Method: A simple eight-layered mathematical model for intraretinal oxygen partial pressure distribution was developed using Fick's law of diffusion, Michaelis-Menten kinetics, and oxygen delivery in the inner retina. The system of non-linear differential equations was solved numerically using Runge-kutta Nystroms method. Result: The model predicts that a decrease in the blood flow rate reduces the partial pressure of oxygen in adapted conditions of light and darkness. It was also observed that the partial pressure of oxygen was higher in adapted light conditions than in adapted dark conditions. Conclusion: The partial pressure of oxygen observed in different layers of the retina was reduced by a decrease in the blood flow rate in the inner retina. The pressure becomes minimum when there is no blood flow in the inner retina. This minimum pressure may fall below the critical level of oxygen partial pressure and affect the retinal function. In order to restore normal retinal function, extreme hyperoxia may assist to make the choroid capable of supplying oxygen to the whole retina during total retinal artery occlusion. Keywords: Mathematical modeling, Intraretinal oxygen pressure, Retinal capillaries, Oxygen consumption, Retinal vascular occlusion, Oxygen metabolism.Tropical Journal of Pharmaceutical Research Vol. 7(4) 2008: pp. 1107-1116