Retinal Micro Research Articles

Protective Effects of Bioactive Compound-Derived Nanoparticle Against Diabetic Retinopathy Through the Modulation of the NF-κB Signaling Pathway.

Diabetic retinopathy is a prevalent and severe microvascular complication of diabetes, often causing visual impairment and blindness in adults. This condition significantly impacts the quality of life for many diabetes patients worldwide. Berberine (BBR), a bioactive compound known for its effects on blood glucose levels, has shown promise in managing diabetic complications. However, the exact mechanism of how BBR influences the development of diabetic retinopathy remains unclear. In this study, we focused on synthesizing a formulation derived from BBR and assessing its protective effects against diabetic retinopathy. The formulation was created using a green synthesis method and thoroughly characterized. In vitro studies demonstrated the antioxidant activity of the formulation against 2,2-diphenyl-1-picryl-hydrazyl-hydrate. We also examined the NF-κB signaling pathway at a molecular level using real-time polymerase chain reaction. To mimic diabetic retinopathy in a controlled setting, a diabetic rat model was established through streptozotocin injection. The rats were divided into normal, diabetic, and treatment groups. The treatment group received the formulated treatment via intragastric administration for several weeks, while the other groups received normal saline. Evaluation of histopathological characteristics and microstructural changes in the retina using hematoxylin and eosin staining revealed that the bioactive compound-derived nanoparticle exhibited favorable biological, chemical, and physical properties. Treatment with the formulation effectively reduced oxidative stress induced by diabetes and inhibited the NF-κB signaling pathway in the diabetic rat model. Under high glucose conditions, oxidative stress was heightened, leading to mitochondria-dependent cell apoptosis in Müller cells via the activation of the NF-κB signaling pathway. The bioactive compound-derived formulation counteracted these effects by decreasing IκB phosphorylation, preventing NF-κB nuclear translocation, and deactivating the NF-κB signaling pathway. Furthermore, treatment with the bioactive compound-derived formulation mitigated retinal micro- and ultrastructural changes associated with diabetic retinopathy. These results indicate that the formulation protects against diabetic retinopathy by suppressing oxidative stress, reducing cell apoptosis, and deactivating the NF-κB signaling pathway. This suggests that the bioactive compound-derived formulation could be a promising therapeutic option for diabetic retinopathy.

Administration of dutasteride in animal models of retinitis pigmentosa

AbstractPurpose: Retinitis pigmentosa (RP) describes a large group of hereditary retinopathies. It mainly affects the rods. However, once the rods have degenerated, the cones, also die, leading to complete blindness. Although, the mutations that cause RP have been identified in different genes, the mechanisms that cause the death of photoreceptor cells are still unknown. Gonadal hormones may play a protective role in RP. Our research group has shown that oral administration of progesterone to RP mice significantly conserves the number of photoreceptors. 5α‐reductase inhibitors (such as dutasteride (DUT)) are approved treatments for androgenic alopecia. Modulation or inhibition of 5α‐reductase activity increases the levels of the neuroprotective steroid progesterone and 17β‐estradiol. The purpose of this study was to administer DUT to RP mice. This may be another form of increasing progesterone levels in the retina and therefore, may be neuroprotective.Methods: Animals were treated in accordance with the ARVO statement for the use of animals. rds mice were treated intraperitoneally with DUT and euthanized on day 21. Haematoxylin–eosin, cell death, and rod and cone immunohistochemistry were performed to determine if DUT was able to delay photoreceptor death. Immunohistochemical techniques were used to study changes in retinal microglia (Iba‐1) and macroglial cells. Neuronal nitric oxide synthase (nNOS) was also quantified.Results: DUT increased photoreceptor survival in rds mice. An increase in iba‐1 positive cells was found in rds retinas and DUT normalized the number, migration and the length and number of branches in these cells. DUT decreased GFAP (glial fibrillar acid protein) expression. We have also observed a slightly increase in nNOS expression in rds mice. DUT administration was also able to decrease nNOS expression.Conclusions: DUT may be used to improve cell survival, to ameliorate retinal micro and macroglial activation as well as alterations in nNOS in RP.

PCAT-UNet: UNet-like network fused convolution and transformer for retinal vessel segmentation.

The accurate segmentation of retinal vessels images can not only be used to evaluate and monitor various ophthalmic diseases, but also timely reflect systemic diseases such as diabetes and blood diseases. Therefore, the study on segmentation of retinal vessels images is of great significance for the diagnosis of visually threatening diseases. In recent years, especially the convolutional neural networks (CNN) based on UNet and its variant have been widely used in various medical image tasks. However, although CNN has achieved excellent performance, it cannot learn global and long-distance semantic information interaction well due to the local computing characteristics of convolution operation, which limits the development of medical image segmentation tasks. Transformer, currently popular in computer vision, has global computing features, but due to the lack of low-level details, local feature information extraction is insufficient. In this paper, we propose Patches Convolution Attention based Transformer UNet (PCAT-UNet), which is a U-shaped network based on Transformer with a Convolution branch. We use skip connection to fuse the deep and shallow features of both sides. By taking advantage of the complementary advantages of both sides, we can effectively capture the global dependence relationship and the details of the underlying feature space, thus improving the current problems of insufficient extraction of retinal micro vessels feature information and low sensitivity caused by easily predicting of pixels as background. In addition, our method enables end-to-end training and rapid inference. Finally, three publicly available retinal vessels datasets (DRIVE, STARE and CHASE_DB1) were used to evaluate PCAT-UNet. The experimental results show that the proposed PCAT-UNET method achieves good retinal vessel segmentation performance on these three datasets, and is superior to other architectures in terms of AUC, Accuracy and Sensitivity performance indicators. AUC reached 0.9872, 0.9953 and 0.9925, Accuracy reached 0.9622, 0.9796 and 0.9812, Sensitivity reached 0.8576, 0.8703 and 0.8493, respectively. In addition, PCAT-UNET also achieved good results in two other F1-Score and Specificity indicators.

Modified capsulorhexis for fiuid-filled mature cataracts.

The aim of this study was to develop a modified capsulorhexis technique featuring a new maneuver for the removal of subcortical fluid in fluid-filled mature cataracts to avoid high intralenticular pressure. This prospective interventional study included 33 eyes with mature cataracts and evidence of subcapsular fluid spaces by slit lamp examination. For each patient, 20% mannitol was administered intravenously according to the bodyweight 1 h preoperatively. Under peribulbar anesthesia, a 2.2-mm main incision was made, and the anterior chamber was filled with a dispersive ophthalmic viscosurgical device. Using a bent-tip cystotome, a 2-mm curved incision was made in the center of the anterior capsule, which released subcortical fluid and was drained through compression of the posterior lip of the main incision using a spatula. Then, fine gentle milking in all quadrants around the puncture on the anterior lens capsule from the periphery toward the site of puncture using the blunt-edged spatula further assists drainage of subcortical fluid and breaks fine septa inside the lens to remove fluid from intralenticular fluid pocket collections. The study included 15 (45.5%) men and 18 (54.5%) women with a mean (standard deviation [SD]) of age of 63.2 (5.33) and 64.4 (6.21) years, respectively. The modified capsulorhexis technique was performed for 33 intumescent cataracts. Capsulorhexis was completed in all cases; capsulorhexis was easy in 31 (94%) eyes and difficult in 2 (6%) eyes. In the two difficult cases, radial extension occurred in one eye, and it was retrieved using the Little technique; the other case with radial tear was completed successfully using a retinal micro scissor from the other edge of the capsulorhexis until reaching an oval, continuous capsulorhexis. This modified capsulorhexis technique with compression on the posterior lip of the main incision and capsule milking allowed for a safe, continuous curvilinear capsulorhexis. Further comparative studies are necessary to confirm our preliminary results.

Hyaluronic-Coated Albumin Nanoparticles for the Non-Invasive Delivery of Apatinib in Diabetic Retinopathy

PurposeApatinib (Apa) is a novel anti-vascular endothelial growth factor with the potential to treat diabetic retinopathy (DR); a serious condition leading to visual impairment and blindness. DR treatment relies on invasive techniques associated with various complications. Investigating topical routes for Apa delivery to the posterior eye segment is thus promising but also challenging due to ocular barriers. Hence, the study objective was to develop Apa-loaded bovine serum albumin nanoparticles (Apa-BSA-NPs) coated with hyaluronic acid (HA); a natural polymer possessing unique mucoadhesive and viscoelastic features with the capacity to actively target CD44 positive retinal cells, for topical administration in DR.MethodsApa-BSA-NPs were prepared by desolvation using glutaraldehyde for cross-linking. HA-coated BSA-NPs were also prepared and HA: NPs ratio optimized. Nanoparticles were characterized for colloidal properties, entrapment efficiency (EE%), in vitro drug release and mucoadhesive potential. In vitro cytotoxicity on rabbit corneal epithelial cells (RCE) was assessed using MTT assay, while efficacy was evaluated in vivo in a diabetic rat model by histopathological examination of the retina by light and transmission electron microscopy. Retinal accumulation of fluorescently labeled BSA-NP and HA-BSA-NP was assessed using confocal microscope scanning.ResultsApa-HA-BSA-NPs prepared under optimal conditions showed size, PdI and zeta potential: 222.2±3.56 nm, 0.221±0.02 and −37.3±1.8 mV, respectively. High EE% (69±1%), biphasic sustained release profile with an initial burst effect and mucoadhesion was attained. No evidence of cytotoxicity was observed on RCE cells. In vivo histopathological studies on DR rat model revealed alleviated retinal micro- and ultrastructural changes in the topical HA-Apa-BSA-NP treated eyes with normal basement membrane and retinal thickness comparable to normal control and intravitreally injected nanoparticles. Improved retinal accumulation for HA-BSA-NP was also observed by confocal microscopy.ConclusionFindings present HA-Apa-BSA-NPs as a platform for enhanced topical therapy of DR overcoming the devastating ocular complications of the intravitreal route.

Retinal Microvascular Response to Short-Term Exposure to Particulate Matters As an Indicator of Cardiovascular Effects in Work Environments

Introduction: According to the literature, Central Retinal Arteriolar Equivalent (CRAE), Central Retinal Venular Equivalent (CRVE), and Artemio Venule Ratio (AVR) are three important markers in determining the changes of retinal artery. These markers are employed as an indicator of cardiovascular effects in workers. This study aimed to evaluate the changes in retinal micro vascular responses in workers exposed to short-term exposure to particulate matters caused by occupational processes using CRAE, CRVE, and AVR markers. Materials and Methods: In this study, 96 workers exposed to job-related pollution in a tile and ceramic company were investigated. Fundus photos of these people were analyzed via ARIA software using the related protocols. The data were investigated employing Kolmogorov–Smirnov and Mann-Whitney tests as well as the correlation and regression tests. Results: No significant difference was observed in the ocular parameters of smokers and non-smokers. Cardiovascular parameters had no significant correlation with CRAE and CRVE as well as breathable and inhalable dust; however, these parameters had a direct and significant correlation with AVR, PM10, and PM2.5 particles. Conclusion: The results did not show any changes in the retinal artery in workers who were exposed to job-related pollution. Moreover, no significant relationship was found between retinal artery changes and cardiovascular parameters. However, more large-scale studies are needed to clarify the relationship of particulate air pollutants with CRAE, CRVE, and AVR changes.

Idiopathic Intracranial Hypertension and Endoscopic Optic Nerve Sheath Fenestration.

Idiopathic intracranial hypertension (IIH), also called as benign intracranial hypertension is a disorder, which is considered benign in its course except its' ill effects on vision. Ocular findings in IIH such as papilledema, macular changes, retinal micro haemorrhages, cotton wool spots and tortuosity of vessels are the prominent features in funduscopy examination in these patients. Papilledema is a hallmark feature for evaluation of response to treatment. Ophthalmological rescue is a primary goal of management of idiopathic intracranial hypertension. Among the treatment options described in literature, optic nerve sheath fenestration is a minimally invasive endoscopic technique for therescue of vision. We present this case-report, which will help ophthalmologists and the surgeons to determine the significance of the funduscopy changes after optic nerve sheath fenestration and help in decision making.

OCT-Angiography Comparison between Obstructive Sleep Apnea Children and Normal Subjects in China

ABSTRACT Purpose Using optical coherence tomography angiography (OCT-A) to compare the retinal micro vessel alteration between obstructive sleep apnea (OSA) children and normal subjects. Methods One hundred-thirty-two eyes (132 participants) were recruited in this study. The average age of OSA group (66 eyes) and healthy control group (66 eyes) were 6.23 ± 1.73 and 6.76 ± 1.89 years, respectively. The retinal vascular network density indices and the fovea avascular zone (FAZ) size were analyzed by OCT-A. Results All of the OCT-A parafoveal vessel indices, including the vascular diameter (VD), vascular area density (VAD), vascular skeleton density (VSD), and vessel perimeter index (VPI) in the macular superficial/deep capillary plexus (SCP/DCP) as well as the FAZ in the DCP, were significantly lower in the OSA group than in the control group (p < .05). The four parafoveal quadrants indices (temporal, superior, nasal, and inferior) of VD and VAD in both the two layer were significantly lower in the OSA group than in control group (p < .05). However, the differences of VSD and VPI indices in the SCP/DCP did not show statistical significant changes. Conclusion The intermittent hypoxia in children with OSA might influence the retinal capillary vascular supply. We speculate that the indices of the quadrants are lower in OSA children compared with those in healthy controls, which may be due to the change of the retinal metabolic demands. OCT-A is an ideal method to evaluate the retinal alterations in pediatric OSA. Abbreviations OCT-A: optical coherence tomography angiography; OSA: obstructive sleep apnea; FAZ: fovea avascular zone; VD: vascular diameter; VAD: vascular area density; VSD: vascular skeleton density; VPI: vessel perimeter index; SCP/DCP: superficial/deep capillary plexus; BCVA: best corrected visual acuity; SE: spherical equivalent; AL: ocular axial length; T: temporal; N: nasal; (S): superior; (I): inferior; (SD): standard deviation

Electroretinogram and Visual Evoked Potentials in Patients with Type ll Diabetes Mellitus

Background: Retinopathy is a severe and common complication of diabetes. The pathology seems to be characterized not only by the involvement of retinal micro vessels but also by a real neuropathy. Before the onset of micro vascular lesions, the retina of the eye undergoes subtle functional changes that are not detectable by fundus photography. Electrophysiological investigations allow a more detailed study of the visual function. These techniques are safe, repeatable, quick, and objective. Objective: To study pattern electroretinogram (PERG) and pattern reversal visual evoked potentials (PRVEP) in type 2 diabetic patients without diabetic retinopathy (DR) or with mild non-proliferative DR (mNPDR) to detect changes by comparing with those of healthy control. And to assess the correlation of the parameters with diabetes duration and the level of Glycosylated Haemoglobin A1c (HbA1c). Materials and Methods: It was a cross-sectional study, included two groups (diabetic patients and the healthy). Age range was preset at 40-65 years. For all the participants, a detailed clinical history was collected, a comprehensive ophthalmic examination and thorough blood investigations were performed, then {PRVEP (60', 15'), PERG} were recorded and (waveform, peak time, amplitude) of tests components were analyzed. Results: Mean (P100, N135) peak times of PRVEP were statistically significantly delayed in (50) eyes of type 2 diabetics without DR when compared to (36) eyes of control (p-value<0.01), abnormalities in waveforms like (double peaks, broad peak) were also observed in diabetics. There were alterations in other parameters (amplitudes of PRVEP, peak times and amplitudes of PERG) but the changes were not statistically significant. No statistically significant changes were found in (6) eyes of diabetic patients with mNPDR. No statistically significant correlation was obtained between diabetes duration or the level of HbA1c and delay of peak times or reduce amplitudes in patients. Conclusions: Electrophysiological tests are sensitive and useful investigations for the early identification of visual dysfunctions before the development of overt retinopathy in type 2 diabetics. PRVEP is more sensitive than PERG to monitor alterations and it may be sufficient to screen the patients in this stage.

A novel artificial neural network-based algorithm for detecting vascular occlusive diseases in retinal images

Introduction: Central retinal vascular occlusions cause sudden painless complete blindness of one eye or partial visual loss, depending on the retinal vessel involved. These acute conditions may occur due to thrombosis, diabetic retinopathy, hypertensive retinopathy, glaucoma or due to other systemic conditions like connective tissue disorders. Central retinal artery occlusion (CRAO) is considered analogous to a cerebral stroke and it is an ophthalmological emergency. Central retinal vein occlusion (CRVO) is one of the most common causes of visual loss worldwide and the second most common cause of blindness due to retinal vascular disorders after diabetic retinopathy. Artificial intelligence (AI) based methodologies have been used in automated diagnosis support systems in detecting many ophthalmological conditions like diabetic retinopathy, retinal micro aneurisms, and retinal haemorrhages. Methods: The developed algorithm consists of modules for, image pre-processing, extraction of the areas of interest, feature extraction, feature presentation and image classification. A feed-forward back-propagation multilayer artificial neural network (ANN), with 27 input layer neurones, three output layer neurones and 81 first hidden layer and nine second hidden layer neurones, was used as the image classifier. This methodology was trained with 90 retinal images. Results: The percentage accuracy of the developed ANN-based ophthalmological image classification algorithm is 97.8% when it is trained to diagnose CRAO and CRVO. The sensitivity is 98.3%, and the specificity is 100%. Conclusions: This study presents the first AI-based approach in automatic detection of both CRAO and CRVO. Once this algorithm is trained to minimise false negatives, it can be used as an automated diagnosis support system in ophthalmological screening programs.

Neuroprotective effect of insulin-loaded chitosan nanoparticles/PLGA-PEG-PLGA hydrogel on diabetic retinopathy in rats.

BackgroundTo pursuit effective sustained release systems for insulin to treat diabetic retinopathy (DR), a novel insulin delivering system was developed via loading onto chitosan nanoparticles/poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid) hydrogel (ICNPH).Methods and materialsExaminations including electroretinography, HE staining, transmission electron microscopy, terminal deoxynucleotidyl transferased UTP nick-end labeling, immunofluorescence, Western blot, and real-time polymerase chain reaction were performed to evaluate the neuroprotective efficacy of ICNPH on DR by a single subconjunctival injection.ResultsCompared with the insulin, blank, and sham treatment groups, subconjunctival injection of ICNPH significantly reduced the decrease of scotopic B-wave amplitude, alleviated retinal micro- and ultrastructural changes, and reduced retinal cell apoptosis caused in DR rats. Meanwhile, a significant reduction of vascular endothelial growth factor and glial fibrillary acidic protein expression as well as a remarkable increase in Occludin expression was also found in retinas in ICNPH group compared with the sham treatment group.ConclusionThe results indicate that ICNPH has sufficient neuroprotective effect on retinas through subconjunctival injection in DR rats and facilitates controlled insulin delivery. It might be one of the therapeutic strategies for DR in the near future.

The expression of retinal micro RNA evoked by hyperglycemia and after adiponectin treatment in human retinal endothelial Cells

The expression of retinal micro RNA evoked by hyperglycemia and after adiponectin treatment in human retinal endothelial Cells

The Preschool Activity, Technology, Health, Adiposity, Behaviour and Cognition (PATH-ABC) cohort study: rationale and design

BackgroundPrevalence estimates internationally suggest that many preschool-aged children (3–5 years) are insufficiently physically active and engage in high levels of screen-based entertainment. Early childhood is the developmental period for which we know the least about the effects of physical activity on development and health. Likewise, rapid technological advancements in mobile electronic media have made screen-based forms of entertainment for young children ubiquitous, and research demonstrating the impacts on cognition, psychosocial well-being, and health has lagged behind the rate of adoption of these technologies. The purpose of the Preschool Activity, Technology, Health, Adiposity, Behaviour and Cognition (PATH-ABC) study is to investigate if physical activity and screen-based entertainment are independently associated with cognitive and psychosocial development, and health outcomes in young children, and if so, how much and which types of these behaviours might be most influential.MethodsThe PATH-ABC study is a prospective cohort, aiming to recruit 430 3–5 year-old children. Children are recruited through and complete initial assessments at their Early Childhood Education and Care (ECEC) centre, and then 12-months later at their centre or school. Direct assessments are made of children’s habitual physical activity using accelerometry, cognitive (executive function) and language development (expressive vocabulary), psychosocial development (emotional understanding, Theory of Mind, empathy, and heart rate variability), adiposity (body mass index and waist circumference), and cardiovascular health (blood pressure and retinal micro- vasculature). Educators report on children’s psychological strengths and difficulties and self-regulation. Parents report on children’s habitual use of electronic media and other child, parent and household characteristics.DiscussionThe PATH-ABC study aims to provide evidence to enhance understanding of how much and which types of physical activity and screen-based media influence development and health in preschool-aged children. This information would benefit parents, educators, health professionals and governments seeking to develop strategies and policies to give young children the best start in life by promoting healthy levels of physical activity and electronic media use.

Differences in gene expression profiles of hypoxic human embryonic retinal microvascular endothelial cells induced by cobalt chloride

Objective To study the differentially expressed genes and analyze its functional pathways of retinopathy of prematurity(ROP), in order to discover the pathogenesis and provide the theoretical basis for the prevention and treatment of ROP. Methods Fetal eyeballs of induced labor were obtained and retinal microvascular endothelial cells were isolated and cultured.The endothelial cells were divided into 7 groups according to the medium of cobalt chloride (CoCl2) concentration (0 μmol/L, 100 μmol/L, 150 μmol/L, 200 μmol/L, 250 μmol/L, 300 μmol/L, 350 μmol/L), and 150 μmol/L CoCl2 was finally used to induce ROP model in vitro.Retinal microvascular endothelial cells were verified by adopting Ⅷ factor and CD31 antibody fluorescence staining.RNA purification, gene chip hybridization and signi-ficant analysis of microarrays were performed to screen differentially expressed genes.Genes functional pathways were studied by using gene ontology analysis software. Results (1) The proliferation activity of vascular endothelial cells decreased when CoCl2≥150 μmol/L(F=21, P<0.05). (2) In 150 μmol/L CoCl2 group, blue nucleus and green cytoplasm were visible in the second and the third generation vascular endothelial cells stained by factor Ⅷ antibody, and red fluorescence could also be observed in the cytoplasm by means of CD31 monoclonal antibody staining.However, only blue nucleus was detected in the group without CoCl2.(3)There were 326 genes differently expressed in retinal micro vascular endothelial cells induced by CoCl2in vitro, among whom, 198 genes were up-regulated and 128 genes were down-regulated.Up-regulated expression genes were 1.5 times more than those of the down-regulated genes.(4)Ten biological pathways including cell hypoxia, angiogenesis suppression and iron ion transport etc.may play important roles in ROP pathogenesis. Conclusions Hypoxic retinal microvascular endothelial cells induced by CoCl2 can successfully be used to induce cell model of ROP in vitro.Differentially expressed genes may play an important role in ROP development.Functional pathway such as hypoxic cells, inhibition of angiogenesis, iron ion transport may be associated with ROP pathogenesis. Key words: Cobalt chloride; Retinopathy of prematurity; Gene expression profile

Automatic Exudates Detection in Diabetic Retinopathy Images

Diabetic Retinopathy (DR) refers to the presence of typical retinal micro vascular lesions in persons with diabetics. When the disease is at the early state, a prompt diagnosis may help in preventing irreversible damages to the diabetic eye. If the exudates are closer to macula, then the situation is critical. Early detection can potentially reduce the risk of blind. This paper proposes tool for the early detection of Diabetic Retinopathy using edge detection, algorithm kmeans in segmentation phase, invariant moments (Hu and Affine) and descriptor GIST in extraction phase. In the recognition phase, neural network is adopted. All tests are applied on database DIARETDB1.

Emerging Role of VEGFC in Pathological Angiogenesis

Emerging Role of VEGFC in Pathological Angiogenesis

Optic Disc Detection and Blood Vessel Diameter Estimation in Patients with Diabetics Mellitus, using Digital Color Funds Images

Optic disc detection and retinal vessel diameter measurement are important tasks in the studies of the association of retinal micro vascular disease with ocular effects, such as cerebral atrophy, cognitive decline, stroke, diabetes and hypertension. This work presents an automatic detection of optic disc irregularities, and determines an appropriate region of interest for retinal vessel diameter measurement. We measured the retinal vessel diameters in 44 diabetic and 60 normal images captured from human eye fundus images with three parameters: Main retinal artery equivalents, Main retinal vein equivalents, and artery to vein diameter ratio. The average of the main artery equivalents in patients with diabetes mellitus is 8.48 pixels, and the average of main vein equivalents is 11.63 pixels. The average of main artery equivalents in healthy people is 9.57 pixels and the average of main vein equivalents is 12.03 pixels. The average ratio of arteriole to vein diameter is about 0.75 in patients’ images with diabetes and approximately 0.80 in healthy people. The results show that the average ratio of arteriole to vein diameter in diabetic patients is smaller than that of healthy people.

Mapping the time line of senescent changes in human retinal histology from third to tenth decade

IntroductionRetinal pathologies causing irreversible visual loss are very common in India especially in advance age. Increased understanding of the age related structural and functional changes in retina can immensely help in better diagnostic and therapeutic modalities. MethodsTwenty five human retinal tissues from 21 years to 99 years of age were studied histologically and changes seen with H&E staining, in each retinal layer, are described. Special stains and specific immune labelled antibodies were used to understand the changes better. ResultsRetinal pigment epithelium showed, gradual reduction in cell size, melanin granules and increase in lipofuscin content & increase in bruch's membrane hyalinization with age. As age advanced there was reduction in the ratio of the rods and cones, thickness of the outer plexiform layer, ganglion cell count and thickness of the nerve fibre layer. The thicknesses of all the retinal layers and the ganglion cell count have been documented decade wise. ConclusionsThis detailed description may aid in improved management of diseases that are characterized by abnormal or premature aging as well as in understanding the age related retinal disorders. This data will also improve the interpretations of images of retinal micro anatomy obtained in patients by spectral domain-optical coherence tomography (SD-OCT), routinely used by ophthalmologists.

Evaluation of anti-HIF and anti-angiogenic properties of honokiol for the treatment of ocular neovascular diseases.

Pathological activation of the hypoxia-inducible-factor (HIF) pathway leading to expression of pro-angiogenic genes, such as vascular endothelial growth factor (VEGF), is the fundamental cause of neovascularization in ocular ischemic diseases and cancers. We have shown that pure honokiol inhibits the HIF pathway and hypoxia-mediated expression of pro-angiogenic genes in a number of cancer and retinal pigment epithelial (RPE) cell lines. The crude extracts, containing honokiol, from Magnolia plants have been used for thousands of years in the traditional oriental medicine for a number of health benefits. We have recently demonstrated that daily intraperitoneal injection of honokiol starting at postnatal day (P) 12 in an oxygen induced retinopathy mouse model significantly reduced retinal neovascularization at P17. Here, we evaluate the mechanism of HIF inhibition by honokiol in RPE cells. Using chromatin immunoprecipitation experiments, we demonstrate that honokiol inhibits binding of HIF to hypoxia-response elements present on VEGF promoter. We further show using a number of in vitro angiogenesis assays that, in addition to anti-HIF effect, honokiol manifests potent anti-angiogenic effect on human retinal micro vascular endothelial cells. Our results suggest that honokiol possesses potent anti-HIF and anti-angiogenic properties. These properties of honokiol make it an ideal therapeutic agent for the treatment of ocular neovascular diseases and solid tumors.

Retinal vasculopathies

AbstractDrug‐induced retinal vasculopathies constitute a group of rare disorders, most often produced by quinine, aminoglycosides, hormone preparations, and interferon. IFN‐ associated retinopathy includes cotton wool spots, retinal hemorrhages and retinal micro aneurysms. Aminoglycosides were often used subconjunctivally after different ocular surgeries as a postoperative prevention of endophthalmitis and intravitreally as a method of endophthalmitis treatment. Both clinical and animal studies have shown vascular changes, including whitening of the retina, retinal hemorrhages, multiple areas of vascular leakage and macular infarction. Although the true pathogenesis remains unknown, the clinical presentation of capillary nonperfusion has suggested a primarily vascular mechanism. The mechanism of quinine‐induced retinal toxicity, although still not well understood, includes probably ischemic/ occlusive type of events occurring in the posterior retinal circulation with relative sparing of choroidal circulation. Hormone‐related retinopathy, mainly due to oral contraceptives, include among others retinal hemorrhage or emboli, macular edema, and papillary edema.