Pathophysiology of Diabetic Retinopathy: The Old and the New

Vision loss in diabetic retinopathy (DR) is ascribed primarily to retinal vascular abnormalities—including hyperpermeability, hypoperfusion, and neoangiogenesis—that eventually lead to anatomical and functional alterations in retinal neurons and glial cells. Recent advances in retinal imaging systems using optical coherence tomography technologies and pharmacological treatments using anti-vascular endothelial growth factor drugs and corticosteroids have revolutionized the clinical management of DR. However, the cellular and molecular mechanisms underlying the pathophysiology of DR are not fully determined, largely because hyperglycemic animal models only reproduce limited aspects of subclinical and early DR. Conversely, non-diabetic mouse models that represent the hallmark vascular disorders in DR, such as pericyte deficiency and retinal ischemia, have provided clues toward an understanding of the sequential events that are responsible for vision-impairing conditions. In this review, we summarize the clinical manifestations and treatment modalities of DR, discuss current and emerging concepts with regard to the pathophysiology of DR, and introduce perspectives on the development of new drugs, emphasizing the breakdown of the blood-retina barrier and retinal neovascularization.

Unlocking the Neurogenic Potential of Mammalian Müller Glia

Müller glia (MG) are the primary support cells in the vertebrate retina, regulating homeostasis in one of the most metabolically active tissues. In lower vertebrates such as fish, they respond to injury by proliferating and reprogramming to regenerate retinal neurons. In mammals, MG may also react to injury by proliferating, but they fail to initiate regeneration. The barriers to regeneration could be intrinsic to mammalian MG or the function of the niche that cannot support the MG reprogramming required for lineage conversion or both. Understanding these mechanisms in light of those being discovered in fish may lead to the formulation of strategies to unlock the neurogenic potential of MG and restore regeneration in the mammalian retina.

Clinical and therapeutic correlations in patients with slight acute pancreatitis / Correlações clínico-terapêuticas em pacientes com pancreatite aguda leve

BACKGROUND: Acute pancreatitis is an inflammatory disease of the pancreas due to enzymatic autodigestion which can cause necrosis or multiple organ failure; its pathophysiology is not fully known yet. AIM: To evaluate the correlation between clinical and therapeutic data in patients with mild acute pancreatitis. METHODS: A retrospective study in 55 medical records of patients admitted with acute mild pancreatitis was realized to analyze the association between age, leukocytosis, serum glutamic-oxaloacetic transaminase and lactate dehydrogenase, glucose, antibiotics, time admission and Ranson´s scores. RESULTS: There was a positive association between less intensive care (strict hydration, analgesia and monitoring of vital signs), early antibiotic therapy (monotherapy), early return to diet after 48 hours and laboratory control of the serum amylase and lipase (high in the first week and decreasing after 10 days, without any prognostic value). CONCLUSIONS: Changes in the management of patients with mild acute pancreatitis, such as enteral nutrition, rational use of lower spectrum antibiotics and intensive care, have contributed significantly to the reduction of hospitalization time and mortality. .

RACIONAL: Pancreatite aguda consiste de doença inflamatória do pâncreas por autodigestão enzimática que pode ocasionar necrose ou mesmo falência múltipla de órgãos e de fisiopatologia ainda não totalmente conhecida. OBJETIVO: Avaliar as correlações existentes entre dados clínicos e terapêuticos em pacientes com pancreatite aguda leve. MÉTODOS: Foi realizado estudo retrospectivo em 55 prontuários de pacientes internados por pancreatite aguda leve para análise de associação entre idade, leucocitose, dosagem sérica de transaminase glutâmico-oxalacética e de desidrogenase lática, glicemia, antibioticoterapia, tempo de internação e escores de Ranson. RESULTADOS: Houve associação positiva entre cuidados intensivos menores (hidratação rigorosa, analgesia e monitorização de sinais vitais), antibioticoterapia precoce (monoterapia), retorno precoce da dieta após 48 horas e controle laboratorial dos níveis séricos de amilase e lipase (elevados na primeira semana e decrescentes após 10 dias, porém sem valor prognóstico). CONCLUSÕES: Mudanças no manejo de pacientes com pancreatite aguda leve, tais como nutrição enteral, uso racional de antibióticos de menor espectro e cuidados intensivos têm contribuído significativamente para a redução do tempo de internação e mortalidade. .

Validation of glaucoma-like features in the rat episcleral vein cauterization model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Glaucoma, an irreversible optic nerve neuropathy, always results in blindness. This study aimed to evaluate glaucoma-like features in the rat episcleral vein cauterization (EVC) model by multiple in vivo and in vitro evidences.</p><p><b>METHODS</b>Wistar rat was used in this study. The elevated intraocular pressure (IOP) was induced by cauterization of three episcleral veins. IOP was monitored with Tono-Pen XL tonometer. Time-dependent changes to the neuronal retinal layers were quantified by Fourier domain-optical coherence tomography. The function of retina was evaluated by electroretinogram (ERG). Survival of retinal ganglion cells (RGCs) was quantified by retrograde labeling. Histology study was performed with retinal sections stained with hematoxylin-eosin, glial fibrillary acidic protein, and neuronal nuclear antigen. Retina and aqueous humor protein were extracted and cytotoxic protein tumor necrosis factor alpha (TNF-α) and alpha-2 macroglobulin (α2m) were measured with Western blotting.</p><p><b>RESULTS</b>EVC is a relatively facile intervention, with low failure rates (<5%). After surgical intervention, chronic mild IOP elevation (about 1.6-fold over normal, P < 0.05) was induced for at least 6 weeks without requiring a second intervention. High IOP causes chronic and progressive loss of RGCs (averaging about 4% per week), progressive thinning of neuronal retinal layers (3-5 μm per week), and reduction of a- and b-wave in ERG. EVC method can also induce glial cell activation and alterations of inflammation proteins, such as TNF-α and α2m.</p><p><b>CONCLUSION</b>EVC method can establish a robust, reliable, economic and highly reproducible glaucomatous animal model.</p>

Axonal loss and blood flow disturbances in the natural course of indirect traumatic optic neuropathy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Indirect traumatic optic neuropathy (TON) is an acute injury of the optic nerve associated with severe visual dysfunction, which may be a result of secondary mechanical injury and vascular disorder of the optic nerve due to trauma. We analyzed the natural course of axonal loss and blood flow disturbances in patients with indirect TON to find a possible therapeutic window.</p><p><b>METHODS</b>A cohort of 54 patients with indirect TON recruited between October 2008 and October 2010 at Beijing Tongren Hospital was retrospectively analyzed. The patients were divided into no light perception group (NLP) and better than NLP (btNLP) group. Specifically, the thickness of the retinal nerve fiber layer (RNFL) measured by spectral domain optical coherence tomography (SD-OCT), and hemodynamic parameters of the ophthalmic artery (OA), central retinal artery (CRA) and posterior ciliary artery (PCA) were determined.</p><p><b>RESULTS</b>Two weeks after injury, there was a statistically significant decrease in the thickness of RNFL in the btNLP group as compared with the fellow control eyes (P < 0.05). In contrast, in the NLP group, RNFL thickness slightly increased for 2 weeks following injury, then overtly reduced after 4 weeks (P < 0.05). Peak systolic velocity (PSV) of CRA was significantly decreased 4 weeks after injury (P < 0.05) in both the NLP group and btNLP group (P < 0.05). The thickness of RNFL in the NLP group was negatively correlated with PSV of CRA after 1 week of injury (P < 0.05, r = -0.962).</p><p><b>CONCLUSIONS</b>SD-OCT is a useful supplement in detecting the axonal loss in TON. The dynamic change of the thickness of RNFL appears to correlate with the hemodynamic disturbances in the natural course of TON. The first 2 weeks following an injury is critical and should be considered as the therapeutic window for TON patients.</p>

Retinal nerve fiber layer in primary open-angle glaucoma with high myopia determined by optical coherence tomography and scanning laser polarimetry / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Fundus changes associated with high myopia (HM) may mask those associated with primary open-angle glaucoma (POAG). This study aim to determine the characteristics of RNFL thickness changes in patients with both POAG and HM and compare these to changes in patients with only HM. The diagnostic capabilities of both OCT and GDxVCC in this subset of patients are also evaluated.</p><p><b>METHODS</b>Twenty-two eyes with POAG and HM (spherical equivalent (SE) between -6.0 and -12.0 D) were evaluated, and 22 eyes with HM were used for comparison. Characteristic retinal nerve fiber layer (RNFL) thickness profiles in patients with POAG and HM were examined using optical coherence tomography (OCT) and scanning laser polarimetry with variable corneal compensation (GDxVCC), and the diagnostic capabilities of these imaging modalities were compared. RNFL parameters evaluated included superior average (Savg-GDx), inferior average (Iavg-GDx), temporal-superior-nasal- inferior-temporal (TSNIT) average, and nerve fiber indicator (NFI) on GDxVCC and superior average (Savg-OCT), inferior average (Iavg-OCT), nasal average (Navg-OCT), temporal average (Tavg-OCT), and average thickness (AvgThick-OCT) on OCT (fast RNFL scan). Visual field testing was performed and defects were evaluated using mean defect (MD) and pattern standard deviation (PSD).</p><p><b>RESULTS</b>The RNFL parameters (P < 0.05) significantly different between groups included Savg-GDx, Iavg-GDx, TSNIT average, NFI, Savg-OCT, Iavg-OCT, Tavg-OCT, and AvgThick-OCT. Significant correlations existed between TSNIT average and AvgThick-OCT (r = 0.778), TSNIT average and MD (r = 0.749), AvgThick-OCT and MD (r = 0.647), TSNIT average and PSD (r = -0.756), and AvgThick-OCT and PSD (r = -0.784). The area under the receiver operating characteristic curve (AUROC) values of TSNIT average, Savg-GDx, Iavg-GDx, NFI, Savg-OCT, Iavg-OCT, Navg-OCT, Tavg-OCT, and AvgThick-OCT were 0.947, 0.962, 0.973, 0.994, 0.909, 0.917, 0.511, 0.906, and 0.913, respectively. The NFI AUROC was the highest value.</p><p><b>CONCLUSIONS</b>RNFL thickness was significantly lower in all but the nasal quadrant in patients with POAG and HM, compared to patients with only HM. Measurements with OCT and GDxVCC were well-correlated, and both modalities detected RNFL thickness changes. However, GDxVCC was better than OCT in detecting POAG in HM patients.</p>

Gap Junction Contributions to the Goldfish Electroretinogram at the Photopic Illumination Level

Understanding how the b-wave of the electroretinogram (ERG) is generated by full-field light stimulation is still a challenge in visual neuroscience. To understand more about the origin of the b-wave, we studied the contributions of gap junctions to the ERG b-wave. Many types of retinal neurons are connected to similar and different neighboring neurons through gap junctions. The photopic (cone-dominated) ERG, stimulated by a small light beam, was recorded from goldfish (Carassius auratus) using a corneal electrode. Data were obtained before and after intravitreal injection of agents into the eye under a photopic illumination level. Several agents were used to affect gap junctions, such as dopamine D1 and D2 receptor agonists and antagonists, a nitric oxide (NO) donor, a nitric oxide synthase (NOS) inhibitor, the gap junction blocker meclofenamic acid (MFA), and mixtures of these agents. The ERG b-waves, which were enhanced by MFA, sodium nitroprusside (SNP), SKF 38393, and sulpiride, remained following application of a further injection of a mixture with MFA. The ERG b-waves decreased following NG-nitro-L-arginine methyl ester (L-NAME), SCH 23390, and quinpirole administration but were enhanced by further injection of a mixture with MFA. These results indicate that gap junction activity influences b-waves of the ERG related to NO and dopamine actions.

Optical coherence tomography evaluation of retinal nerve fiber layer in longitudinally extensive transverse myelitis / Avaliação da camada de fibras nervosas da retina na mielite transversal longitudinalmente extensa usando tomografia de coerência óptica

OBJECTIVE: To compare optical coherence tomography (OCT) measurements on the retinal nerve fiber layer (RNFL) of healthy controls and patients with longitudinally extensive transverse myelitis (LETM) without previous optic neuritis. METHOD: Twenty-six eyes from 26 patients with LETM and 26 control eyes were subjected to automated perimetry and OCT for comparison of RNFL measurements. RESULTS: The mean deviation values from perimetry were significantly lower in patients with LETM than in controls (p<0.0001). RNFL measurements in the nasal quadrant and in the 3-o'clock segment were significantly smaller in LETM eyes than in controls. (p=0.04 and p=0.006, respectively). No significantly differences in other RNFL measurements were found. CONCLUSION: Patients with LETM may present localized RNFL loss, particularly on the nasal side of the optic disc, associated with slight visual field defects, even in the absence of previous episodes of optic neuritis. These findings emphasize the fact that patients with LETM may experience attacks of subclinical optic nerve damage.

OBJETIVO: Comparar as medidas da camada de fibras nervosas da retina (CFNR) usando a tomografia de coerência óptica (TCO) em indivíduos normais e pacientes com mielite transversal longitudinalmente extensa (MTLE) sem episódio prévio de neurite óptica. MÉTODO: Vinte e seis olhos de 26 pacientes com MTLE e 26 olhos normais foram submetidos à campimetria computadorizada e TCO para comparação das medidas da CFNR. RESULTADOS: Valores do parâmetro desvio médio da campimetria computadorizada foram significativamente menores nos pacientes com MTLE do que nos controles (p<0,001). Medidas da CFNR no quadrante nasal e no segmento 3 horas foram significativamente menores nos olhos dos pacientes com MTLE do que nos olhos normais (p=0,04 e p=0,006, respectivamente). Não foi encontrada diferença significante nas outras medidas da CFNR avaliadas. CONCLUSÃO: Pacientes com MTLE podem apresentar perda localizada da CFNR, particularmente na região nasal do disco óptico, associada a defeitos discretos de campo visual, mesmo na ausência de episódio prévio de neurite óptica. Estes achados sugerem que pacientes com MTLE podem apresentar acometimento subclínico do nervo óptico.

Morphological and functional evaluation of an animal model for the retinal degeneration induced by N-methyl-N-nitrosourea / 대한해부학회지

The retinal degeneration (RD) is a general cause of blindness. To study its pathophysiology and evaluate the effects of new therapeutic agents before clinical trials, it is essential to establish reliable and stable animal models. This study evaluated a RD animal model in which blindness was induced by N-methyl-N-nitrosourea (MNU), a potent retinotoxin leading to apoptosis of photoreceptors. MNU was applied to the Sprague-Dawley rats by a single intraperitoneal injection in different doses (40, 50, and 60 mg/kg). The retinal functions were examined at 1 week after MNU injection by electroretinogram (ERG). Afterwards, each retina was examined by hematoxylin and eosin stain and immunohistochemistry with anti-glial fibrillary acidic protein antibody. Upon MNU injection of 40, 50 and 60 mg/kg, the ERG amplitude of a-waves showed significant reductions of 7, 26, and 44%, respectively, when compared to that of normal a-waves. The b-wave amplitudes were about 89, 65, and 58% of normal b-waves in the response to scotopic light stimulus. At 1 week, 2 weeks, and 4 weeks after MNU injection (50 mg/kg), all scotopic ERG components decreased progressively. In addition, degeneration of retinal neurons was observed in a time- and dose-dependent manner after MNU injection. Taken together, functional reduction following RD induced by MNU correlates with morphological changes. Thus, this RD rat model may be a useful model to study its pathophysiology and to evaluate the effects of new therapeutic agents before clinical trials.

Spikes with short inter-spike intervals in frog retinal ganglion cells are more correlated with their adjacent neurons' activities

Correlated firings among neurons have been extensively investigated; however, previous studies on retinal ganglion cell (RGC) population activities were mainly based on analyzing the correlated activities between the entire spike trains. In the present study, the correlation properties were explored based on burst-like activities and solitary spikes separately. The results indicate that: (1) burst-like activities were more correlated with other neurons' activities; (2) burst-like spikes correlated with their neighboring neurons represented a smaller receptive field than that of correlated solitary spikes. These results suggest that correlated burst-like spikes should be more efficient in signal transmission, and could encode more detailed spatial information.

Bilateral hypermetropia, myelinated retinal nerve fibers, and amblyopia

A 14-year-old hyperopic female with poor vision in both eyes was evaluated for ophthalmic and systemic diseases. The patient had bilateral retinal fiber myelination and greater vision loss in the more hyperopic eye. This was a rare case of reverse Straatsma syndrome, the clinical presentation which may be accompanied with significant vision loss

Morphological study of retinal neurons after continuous exposure to fluorescent light in adult male albino rats

Retinal function depends on light trapping. However, continuous exposure to light may cause damage to the highly vulnerable retinal structure. This study aimed to investigate the possible histological alterations that might occur in the retinal neurons as a result of continuous exposure to fluorescent light in adult male albino rats. Ten healthy adult male albino rats were equally divided into two groups: a control group and a light-exposed group. Rats of control group were kept in 12 h light/1 2 h dark for 12 weeks. Rats of light-exposed group were put in top-opened cages illuminated by white fluorescent bulbs continuously for 1 week and then were kept in 12 h light/12 h dark for the following 11 weeks. The retina was extirpated and processed for examination by light and electron microscopy. The thickness of outer nuclear, inner nuclear, outer plexiform, and inner plexiform layers was estimated morphometrically and was statistically analyzed. Fluorescent light-exposed neural retina revealed that photoreceptor outer segments were markedly disorganized and inner segments were short and less condensed. Outer nuclear layer containeo few photoreceptors with marked intercellular spaces. Inner nuclear layer showed wide spaces between its neurons, with some of them having shrunken nuclei and others having disintegrated nuclei. Muller cells with deeply stained bodies and processes were seen in inner and outer nuclear layers. Many ectopic neurons were detected in the inner plexiform layer. Ganglion cell layer mostly contained deeply stained glial cells and few ganglion neurons. Nerve fiber layer showed an apparent increase in thickness. The estimated and analyzed thickness of the outer nuclear, inner nuclear, outer plexiform, and inner plexiform layers confirmed the results. Continuous exposure to fluorescent light triggered retinal remodeling, including neuronal loss, reactive gliosis with neuronal and glial cells migration. This may lead to visual impairment

Ribbon Synapses Formed at the Axon of the Calbindin-Immunoreactive ON Cone Bipolar Cell in OFF Sublamina of the Inner Plexiform Layer in the Rabbit Retina / 체질인류학회지

Some retinal neurons, including intrinsically photosensitive retinal ganglion cells have their dendrites stratified in sublamina a of the inner plexiform (IPL), the OFF sublayer, but paradoxically show light-driven ON electrophysiological responses. In order to understand the mechanism on this paradoxical response, by using immunoelectron microscopy with a specific antibody against calbindin, we examined the synaptic connections of the calbindin-immunoreactive ON cone bipolar cell of the rabbit retina, which is thought to make the ribbon synapse in sublamina a of the IPL. The ribbon synapses in sublamina a by calbindin-immunoreactive ON cone bipolar cells were mainly found at the border between the inner nuclear layer and the IPL. Interestingly, the output targets at these ribbon synapses turned out as monads, and multiple synaptic ribbons were engaged in each synapse. These findings were different from those at the conventional ribbon synapse formed by calbindin-immunoreactive ON cone bipolar axon terminals. Thus, these findings may be the characteristics of the calbindin-immunoreactive ON cone bipolar ribbon synapse in sublamina a and can be used to classify the synapse in the retinal circuit research.

Immunohistochemical localization of cyclic AMP-responsive element binding protein (CREB)-binding protein in the pig retina during postnatal development / 대한해부학회지

This study evaluated the cellular localization of cyclic AMP-responsive element binding protein-binding protein (CBP) expression in pig retinas during postnatal development. Immunohistochemistry and Western blot analysis were performed on retinal tissue from 2-day-old, 5-week-old, and 6-month-old pigs. Western blot analysis detected the expression of CBP in the retinas of 2-day-old piglets and showed that it was significantly decreased in the retinas of 5-week-old and 6-month-old pigs. Immunohistochemically, CBP was intensely immunostained in protein kinase C alpha (PKCalpha)-positive-bipolar cells, glutamine synthetase-positive Muller cells, and in ganglion cells in 2-day-old piglets. CBP was detected weakly in the inner plexiform, outer nuclear, and rod and cone layers. CBP immunoreactivity in the ganglion cell layer was decreased in the retinas of 5-week-old and 6-month-old pigs, while clear CBP expression detected in the neurite of PKCalpha-positive bipolar cells in the inner nuclear layer. In addition, CBP immunoreactivity in Muller cells and glial fibrillary acidic protein-positive glial processes was particularly noteworthy in pig retinas, but not in rat retinas. The results indicate that CBP is expressed differentially in the retinal neurons and glial cells according to growth and animal species, and may play an important role in homeostasis in Muller cells, neurite extention in bipolar cells, and signal transduction in photoreceptor cells in the porcine retina.

Effect of erythropoietin on the survival of retinal neurocytes in culture upon serum withdrawal

To clarify whether erythropoietin [EPO] could substitute for the serum component in cultured retinal neurocytes suffering from serum withdrawal. The study was performed in the Shanghai Institute of Traumatology and Orthopedics, Shanghai, China between April 2008 and March 2009. A total of 160 postnatal 2-3 day-old Sprague-Dawley rats were used for this study. After the retinal neurocytes were cultured for 48 hours, the culture media was replaced with serum-free media, and the cells were exposed to 1 U/ml, 3 U/ml, and 6 U/ml EPO for another 24 or 48 hours, the cell body diameter was then assessed using a computerized image-analysis system, and the survival and apoptosis rates of those cells were estimated by method of transcription and translation assay and flow cytometry. Immunocytochemistry was used to detect EPO and erythropoietin receptor [EPOR] expression. The retinal neurocytes had obvious EPO/EPOR expression. The early [p=0.002] and total [p=0.049] apoptosis rates of retinal neurocytes cultured with serum withdrawal were significantly higher than that of neurocytes cultured with serum, and the cell viability of neurocytes cultured with serum withdrawal was significantly lower than that of neurocytes cultured with serum [p=0.047]. The EPO had no effect on the cell body diameter of cultured retinal neurocytes. The cell viability and the apoptosis rates of retinal neurocytes were not significantly different from that of simple serum-withdrawal culture at any EPO concentration. As the addition of EPO immediately after serum withdrawal had no effect in preventing retinal neurocytes apoptosis induced by serum withdrawal, EPO cannot substitute for the serum component

Retinal nerve fiber layer loss documented by optical coherence tomography in patients with optic tract lesions / Perda da camada de fibras nervosas retinianas documentada pela tomografia por coerência óptica em pacientes com lesões do trato óptico

PURPOSE: To report abnormalities of retinal nerve fiber layer (RNFL) thickness using Stratus - optical coherence tomography (OCT) in two patients with optic tract lesions. METHODS: Two patients with long standing homonymous hemianopia from optic tract lesions were submitted to a complete neuro-ophthalmic evaluation and to Stratus -optical coherence tomography examination. RESULTS: Both patients revealed diffuse loss of the RNFL at Stratus - OCT in both eyes. In the eyes with the temporal hemianopia, RFNL loss was diffuse but predominantly in the nasal and temporal areas of the optic disc, the classic pattern of band atrophy of the optic nerve. In the eyes with nasal hemianopia RNFL loss could be documented in the superior and inferior quadrants of the optic disc. RNFL loss correlated well with visual field loss and the expected pattern of RNFL loss in optic tract lesions. CONCLUSION: Stratus-Optical coherence tomography can provide useful information in the diagnosis of optic tract lesions by identifying the characteristic pattern of RNFL loss that occurs in both eyes in this condition.

OBJETIVO: Relatar alterações na camada de fibras nervosas retiniana (CFNR) com o uso da tomografia por coerência óptica (TCO) Stratus em pacientes com lesões do trato óptico. MÉTODOS: Dois pacientes com hemianopsia homônima de longa duração decorrente de lesões do trato óptico foram submetidos a avaliação neuroftalmológica completa e tomografia por coerência óptica Stratus. RESULTADOS: Ambos pacientes demonstraram redução difusa da CFNR nos dois olhos. Nos olhos com a hemianopsia temoporal, a perda da CFNR foi difusa mas com predomínio nas áreas nasal e temporal do disco óptico, um padrão clássico da atrofia em banda do nervo óptico. Nos olhos com hemianopsia nasal observou-se perda da CFNR nos quadrantes superior e inferior do disco óptico. A perda da CFNR se correlacionou com o defeito de campo visual e com o padrão esperado de perda da CFNR nas lesões do trato óptico. CONCLUSÃO: A tomografia por coerência óptica - Stratus pode fornecer informação útil no diagnóstico das lesões do trato óptico ao identificar o padrão característico de perda da CFNR que ocorre em ambos os olhos nesta condição.

Peripapillary retinal nerve fiber layer thickness measurement by three-dimensional optical coherence tomography in a normal population

To determine peripapillary retinal nerve fiber layer [RNFL] thickness values by three-dimensional optical coherence tomography [3D-OCT] in a normal Iranian population and to evaluate the concordance of these measurements with those obtained by the second generation of optical coherence tomography [OCTII]. In a cross-sectional observational study, 96 normal Iranian subjects 20-53 years old were enrolled. Peripapillary RNFL thickness in one randomly selected eye of each subject was measured by 3D-OCT and also by OCT II. Standard achromatic perimetry, corneal pachymetry and A-scan ultrasonographic biometry were also performed. Other study variables included age, gender, laterality [right versus left eye], refractive error, corneal diameter and disc area. Mean peripapillary RNFL thickness measured by 3D-OCT [75.50 +/- 8.38] micro m was significantly less than that measured by OCT II [144.10 +/- 33.32 pn] [P<0.001]. Using 3D-OCT, no significant difference in peripapillary RNFL thickness was observed by gender [P=0.90] or laterality [P=0.17]; RNFL thickness had no correlation with age [P=0.95], axial length [P=0.32], spherical equivalent refractive error [P=0.21], central corneal thickness [P=0.66] and disc area [P=0.31]. However, a positive correlation was found between peripapillary RNFL thickness and corneal diameter [P=0.03]. 3D-OCT seems to yield lower RNFL thickness values as compared to OCT II. It seems advisable to obtain separate baseline measurements when using different generations of OCT machines

Detection of early glaucomatous damage in pseudo exfoliation syndrome by assessment of retinal nerve fiber layer thickness

To detect early glaucomatous changes in pseudo exfoliative patients with normal intraocular pressure [IOP], visual field and optic nerve head appearance; by measuring retinal nerve fiber layer [RNFL] thickness using optical coherence tomography [OCT]. A prospective observational case-control study. Twenty non-glaucomatous [normal IOP, fundus and visual field] pseudo exfoliative patients and 20 age matched healthy control subjects. The RNFL thickness [global and four quadrants] was assessed using combined imaging system OTI [OCT/SLO] and compared with age matched normal control subjects. The RNFL in patients with pseudo exfoliation syndrome [PXS] was significantly thinner in all quadrants except the nasal quadrant compared to the control group [p less than 0.05]. Measurement of RNFL thickness by OCT is useful in detecting early RNFL damage which in turn provides clinically relevant information in detecting early glaucomatous changes in pseudo exfoliative patients

Morphology and Distribution of Gap Junction in Horizontal Cells of the Rabbit Retina / 대한해부학회지

Horizontal cells (HCs) of the mammalian retina are interneurons that provide negative feedback to photoreceptors in the outer plexiform layer (OPL) where the first synapse occurs and contribute to the center surround antagonism that underlies the receptive field properties of many retinal neurons. These functions of HCs are thought to be attributed to their coupled network via gap junctions. Two kinds of connexin (Cx) proteins, Cx50 and 57 are known to form gap junctions of HCs. However, little is known about precise localization of gap junctions within HCs. Thus, this study was designed to determine the localization of HC gap junctions at subcellular level. In vertical ultrathin sections of the rabbit retina, gap junctions composed of Cx50 and 57 were identified in the OPL by the electron-dense reaction products. Each Cx50 and 57 gap junction on putative HC processes showed its own distinct features. Cx50 gap junction was bigger in size and localized more proximally than Cx57. In addition, Cx57 gap junctions had distinct shape. That is, about a half of them appeared to be invaginated or endocytosed in shape. The differences in shape, size and subcellular localization between Cx50 and 57 gap junctions may provide the insights into the function of different types of horizontal cell.

Expression of Substance P in the Experimental Diabetic Rat Retina / 대한해부학회지

Substance P (Sub P) being composed of 11 amino acids sequence is a kind of tachykinin family peptides. It has been known that this substance plays a role of neurotransmitter and/or neuromodulator and is a very potent vascular growth factor in the nervous system. This study has been investigated expression pattern of Sub P in the rat retina at normal and alteration of Sub P expression following diabetic injury using immunohistochemistry. Diabetic condition was induced by a single injection of streptozotocin in Sprague-Dawley rats aged 8 weeks. The animals showing high blood glucose levels (above 300 mg/dL) were cared for 1, 4, 8 and 12 weeks, respectively. The whole-mounted or sectional preparations of the retinas were used for Sub P immunohistochemistry. Sub P immunoreactivity has been localized in subsets of amacrine cells in the inner nuclear layer (INL) and displaced amacrine cells in the ganglion cell layer (GCL) in the normal retina. The dendrites from amacrine cells in the INL were ramified with strata 1 and 3, and those from displaced amacrine cells in the GCL with strata 5 of the inner plexiform layer. Sub P immunoreactive neurons in both the INL and the GCL were more densely populated in the superior half of the retina. During diabetes, the cell number of Sub P immunoreactive neurons was decreased to one third of the normal value at 4 weeks of diabetes and then slightly increased to half of the normal value at 12 weeks of diabetes. In addition, Sub P mRNA levels were reduced at 4 weeks but reincreased at 12 weeks. These results suggest that Sub P in the rat retina at normal state may function differentially in the superior or the inferior halves and Sub P synthetic pathway in the retinal neurons maybe irradiated in earlier stages of diabetic retinopathy.