Severe hypoglycaemia-induced microglial inflammation damages microvascular endothelial cells, leading to retinal destruction.

Human microglia (HMC) are stress-induced inflammatory cells of the retina. It is unknown whether severe hypoglycaemia causes inflammation in microglia, affects the permeability of human retinal microvascular endothelial cells (HRMECs), and causes retinal damage. This study aimed to explore the effects of severe hypoglycaemia on retinal microglial inflammation and endothelial cell permeability and evaluate the damage caused by hypoglycaemia to the retina. The CCK-8 assay was used to measure cell viability. Western blotting was used to detect IL-1ß, IL-6, TNF- α, claudin-1, and occludin expression. ELISA was used to detect IL-1ß, IL-6, and TNF- α. Transmission electron microscopy (TEM) and haematoxylin and eosin staining were used to observe the retinal structure. Immunohistochemistry and immunofluorescence staining assays were also used to detect IL-1ß, IL-6, TNF- α, claudin-1, and occludin expression. Severe hypoglycaemia promoted inflammation in HMC3 cells. Inflammation caused by hypoglycaemia leads to the decreased expression of tight junction proteins. In vivo, severe hypoglycaemia induced structural damage to the retina, increased the expression of inflammatory factors, and decreased the expression of tight junction proteins. Our results suggest that severe hypoglycaemia leads to acute retinal inflammation, affecting the permeability of HRMECs and causing retinal damage.

Characterization of a monkey model with experimental retinal damage induced by N-methyl-D-aspartate.

N-methyl-D-aspartate (NMDA)-induced retinal damage has been well studied in rodents, but the detailed mechanisms have not yet been characterized in nonhuman primates. Here, we characterized the retinal degenerative effects of NMDA on rhesus monkeys in vivo. NMDA saline or saline-only control was injected intravitreally to the randomly assigned eyes and contralateral eyes of four rhesus monkeys, respectively. The structural and functional changes of retina were characterized by optical coherence tomography and electroretinography on days 0, 4, 30 and 60 post injection. Both optic discs and macular areas of the NMDA-injected eyes initially presented with a transient retinal thickening, followed by continued retinal thinning. The initial, transient retinal thickening has also been observed in glaucoma patients, but this has not been reported in rodent NMDA models. This initial response was followed by loss of retina ganglion cells (RGCs), which is similar to glaucomatous optic neuropathy and other RGC-related retinal degenerations. The amplitudes of both the photopic negative response and pattern electroretinogram decreased significantly and remained low until the end of the study. Thus, the NMDA monkey model may serve as a more clinically relevant animal model of retinal damage.

The effect of Fernblock® in preventing blue-light-induced oxidative stress and cellular damage in retinal pigment epithelial cells is associated with NRF2 induction.

Blue light exposure of the ocular apparatus is currently rising. This has motivated a growing concern about potential deleterious effects on different eye structures. To address this, ARPE-19 cells were used as a model of the retinal pigment epithelium and subjected to cumulative expositions of blue light. The most relevant cellular events previously associated with blue-light-induced damage were assessed, including alterations in cell morphology, viability, cell proliferation, oxidative stress, inflammation, and the induction of DNA repair cellular mechanisms. Consistent with previous reports, our results provide evidence of cellular alterations resulting from repeated exposure to blue light irradiation. In this context, we explored the potential protective properties of the vegetal extract from Polypodium leucotomos, Fernblock® (FB), using the widely known treatment with lutein as a reference for comparison. The only changes observed as a result of the sole treatment with either FB or lutein were a slight but significant increase in γH2AX+ cells and the raise in the nuclear levels of NRF2. Overall, our findings indicate that the treatment with FB (similarly to lutein) prior to blue light irradiation can alleviate blue-light-induced deleterious effects in RPE cells, specifically preventing the drop in both cell viability and percentage of EdU+ cells, as well as the increase in ROS generation, percentage of γH2AX+ nuclei (more efficiently with FB), and TNF-α secretion (the latter restored only by FB to similar levels to those of the control). On the contrary, the induction in the P21 expression upon blue light irradiation was not prevented neither by FB nor by lutein. Notably, the nuclear translocation of NRF2 induced by blue light was similar to that observed in cells pre-treated with FB, while lutein pre-treatment resulted in nuclear NRF2 levels similar to control cells, suggesting key differences in the mechanism of cellular protection exerted by these compounds. These results may represent the foundation ground for the use of FB as a new ingredient in the development of alternative prophylactic strategies for blue-light-associated diseases, a currently rising medical interest.

Construction of a screening system for lipid-derived radical inhibitors and validation of hit compounds to target retinal and cerebrovascular diseases.

Recent studies have highlighted the indispensable role of oxidized lipids in inflammatory responses, cell death, and disease pathogenesis. Consequently, inhibitors targeting oxidized lipids, particularly lipid-derived radicals critical in lipid peroxidation, which are known as radical-trapping antioxidants (RTAs), have been actively pursued. We focused our investigation on nitroxide compounds that have rapid second-order reaction rate constants for reaction with lipid-derived radicals. A novel screening system was developed by employing competitive reactions between library compounds and a newly developed profluorescence nitroxide probe with lipid-derived radicals to identify RTA compounds. A PubMed search of the top hit compounds revealed their wide application as repositioned drugs. Notably, the inhibitory efficacy of methyldopa, selected from these compounds, against retinal damage and bilateral common carotid artery stenosis was confirmed in animal models. These findings underscore the efficacy of our screening system and suggest that it is an effective approach for the discovery of RTA compounds.

Effect of hydrogen-rich saline on melanopsin after acute blue light-induced retinal damage in rats.

Excessive exposure to blue light can cause retinal damage. Hydrogen-rich saline (HRS), one of the hydrogen therapies, has been demonstrated to be effective in eye photodamage, but the effect on the expression of melanopsin in intrinsically photosensitive retinal ganglion cells (ipRGCs) is unknown. In this study, we used a rat model of light-induced retinal injury to observe the expression of melanopsin after HRS treatment and to determine the effect of HRS on retinal ganglion cell protection. Adult SD rats were exposed to blue light (48 h) and treated with HRS for 0, 3, 7, and 14 days. Real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB) were performed to find the expression of genes and proteins, respectively. The function of retinal ipRGCs was measured by pattern-evoked electroretinography (pERG). The number and morphological changes of melanopsin-positive ganglion cells in the retina were observed by immunofluorescence (IF). Acute blue light exposure caused a decrease in ipRGC function, decreased expression of melanopsin protein and the melanopsin-positive RGCs, and diminished immunoreactivity in dendrites. However, over time, melanopsin showed a tendency to self-recovery, with an increase in melanopsin protein expression and the number of melanopsin-positive RGCs, with incomplete recovery of function within two weeks. HRS treatment accelerated the recovery process, with a significant increase in melanopsin expression and the number of melanopsin-positive RGCs, and an improvement in the pERG waveform within two weeks.

Diagnosis of retinal damage using Resnet rescaling and support vector machine (Resnet-RS-SVM): a case study from an Indian hospital.

PURPOSE: This study aims to address the challenge of identifying retinal damage in medical applications through a computer-aided diagnosis (CAD) approach. Data was collected from four prominent eye hospitals in India for analysis and model development. METHODS: Data was collected from Silchar Medical College and Hospital (SMCH), Aravind Eye Hospital (Tamil Nadu), LV Prasad Eye Hospital (Hyderabad), and Medanta (Gurugram). A modified version of the ResNet-101 architecture, named ResNet-RS, was utilized for retinal damage identification. In this modified architecture, the last layer's softmax function was replaced with a support vector machine (SVM). The resulting model, termed ResNet-RS-SVM, was trained and evaluated on each hospital's dataset individually and collectively. RESULTS: The proposed ResNet-RS-SVM model achieved high accuracies across the datasets from the different hospitals: 99.17% for Aravind, 98.53% for LV Prasad, 98.33% for Medanta, and 100% for SMCH. When considering all hospitals collectively, the model attained an accuracy of 97.19%. CONCLUSION: The findings demonstrate the effectiveness of the ResNet-RS-SVM model in accurately identifying retinal damage in diverse datasets collected from multiple eye hospitals in India. This approach presents a promising advancement in computer-aided diagnosis for improving the detection and management of retinal diseases.

Establishing chronic models of age-related macular degeneration via long-term iron ion overload.

Age-related macular degeneration (AMD) is characterized by the degenerative senescence in the retinal pigment epithelium (RPE) and photoreceptors, which is accompanied by the accumulation of iron ions in the aging retina. However, current models of acute oxidative stress are still insufficient to simulate the gradual progression of AMD. To address this, we established chronic injury models by exposing the aRPE-19 cells, 661W cells, and mouse retina to iron ion overload over time. Investigations at the levels of cell biology and molecular biology were performed. It was demonstrated that long-term treatment of excessive iron ions induced senescence-like morphological changes, decreased cell proliferation, and impaired mitochondrial function, contributing to apoptosis. Activation of the mitogen-activated protein kinase (MAPK) pathway and the downstream molecules were confirmed both in the aRPE-19 and 661W cells. Furthermore, iron ion overload resulted in dry AMD-like lesions and decreased visual function in the mouse retina. These findings suggest that chronic exposure to overloading iron ions plays a significant role in the pathogenesis of retinopathy and provide a potential model for future studies on AMD.NEW & NOTEWORTHY To explore the possibility of constructing reliable research carriers on age-related macular degeneration (AMD), iron ion overload was applied to establish models in vitro and in vivo. Subsequent investigations into cellular physiology and molecular biology confirmed the presence of senescence in these models. Through this study, we hope to provide a better option of feasible methods for future researches into AMD.

Influence of white-light-emitting diodes on primary visual cortex layer 5 pyramidal neurons (V1L5PNs) and remodeling by blue-light-blocking lenses.

Studies have explored the consequences of excessive exposure to white-light-emitting diodes (LEDs) in the retina. Hence, we aimed to assess the implications of such exposure on structural alterations of the visual cortex, learning and memory, and amelioration by blue-light-blocking lenses (BBLs). Eight-week-old Wistar rats (n = 24) were used for the experiment and divided into four groups (n = 6 in each group) as control, white LED light exposure (LE), BBL Crizal Prevencia-1 (CP), and DuraVision Blue-2 (DB). Animals in the exposure group were exposed to white LED directly for 28 days (12:12-h light/dark cycle), whereas animals in the BBL groups were exposed to similar light with BBLs attached to the LEDs. Post-exposure, a Morris water maze was performed for memory retention, followed by structural analysis of layer 5 pyramidal neurons in the visual cortex. We observed a significant difference (P < 0.001) in the functional test on day 1 and day 2 of training in the LE group. Structural analysis of Golgi-Cox-stained visual cortex layer 5 pyramidal neurons showed significant alterations in the apical and basal branching points (p < 0.001) and basal intersection points (p < 0.001) in the LE group. Post hoc analysis revealed significant changes between (p < 0.001) LE and CP and (p < 0.001) CP and DB groups. Constant and cumulative exposure to white LEDs presented with structural and functional alterations in the visual cortex, which are partly remodeled by BBLs.

Nanosecond multipulse retinal damage thresholds of elongated irradiance profiles in explant measurements and simulations.

Significance: The database for multipulse retinal damage thresholds for the laser safety standard (IEC 60825-1:2014) is confined, especially for elongated irradiation profiles. To ensure eye safety, retinal damage thresholds (ED50 values) need to be determined. Aim: This study aims to examine nanosecond multipulse scenarios. Approach: To determine ED50 values in ex vivo measurements, an optical laser setup is presented. Porcine explant tissue is irradiated with rectangular top-hat profiles. Thermal simulations are carried out on a validated computer model and retinal injury thresholds are obtained. Results: The measurements resulted in ED50 values from 8.46 to 42.72 µJ with a slope from 1.15 to 1.4. A thermal damage in the measurements can be excluded due to the level value in combination with a different type of declining behavior for increasing pulses compared to the simulations. A dependence with increasing elongation or area of the retinal image emerges in the simulations but could not be confirmed in the measurements due to the influencing factors (biological variability, focusing, and measuring procedure). Conclusions: Using slit apertures for beam shaping, variable rectangular spot geometries are realized without changing elements in the setup. For further evaluation of the behavior of elongated irradiation profiles, additional measurements to improve the measurement accuracy are necessary.

Plant bioactive compounds alleviate photoinduced retinal damage and asthenopia: Mechanisms, synergies, and bioavailability.

The retina, an important tissue of the eye, is essential in visual transmission and sustaining adequate eyesight. However, oxidative stress and inflammatory reactions can harm retinal structure and function. Recent studies have demonstrated that exposure to light can induce oxidative stress and inflammatory reactions in retinal cells, thereby facilitating the progression of retinal damage-related diseases and asthenopia. Plant bioactive compounds such as anthocyanin, curcumin, resveratrol, lutein, zeaxanthin, epigallocatechin gallate, and quercetin are effective in alleviating retinal damage and asthenopia. Their strong oxidation resistance and unique chemical structure can prevent the retina from producing reactive oxygen species and regulating eye muscle relaxation, thus alleviating retinal damage and asthenopia. Additionally, the combination of these active ingredients produces a stronger antioxidant effect. Consequently, understanding the mechanism of retinal damage caused by light and the regulation mechanism of bioactive compounds can better protect the retina and reduce asthenopia.

Lutein/Zeaxanthin Isomers and Quercetagetin Combination Safeguards the Retina from Photo-Oxidative Damage by Modulating Neuroplasticity Markers and the Nrf2 Pathway.

Exposure to light-emitting diode (LED) light is a primary cause of retinal damage, resulting in vision loss. Several plant-derived substances, such as lutein and quercetagetin (QCG), show promise in supporting eye health. In this study, the impact of lutein/zeaxanthin (L/Z, Lutemax 2020) and QCG were evaluated individually and together in a rat model of LED-induced retinal damage. A total of 63 Wistar rats were allocated into nine groups (n = 7). For 28 days, the rats received L/Z (10 or 20 mg/kg BW), quercetin (QC, 20 mg/kg BW), QCG (10 or 20 mg/kg BW), or a mixture of different lutein and QCG dosages, after which they were exposed to LED light for 48 h. LED exposure led to a spike in serum malondialdehyde (MDA) and inflammatory cytokines, as well as an increase in retinal NF-κB, ICAM, GFAP, and MCP-1 levels (p < 0.0001 for all). It also reduced serum antioxidant enzyme activities and retinal Nrf2, HO-1, GAP43, NCAM, and outer nuclear layer (ONL) thickness (p < 0.0001 for all). However, administering L/Z and QCG, particularly a 1:1 combination of L/Z and QCG at 20 mg/kg, effectively reversed these changes. The treatment suppressed NF-κB, ICAM, GFAP, and MCP-1 while enhancing Nrf2, HO-1, GAP43, and NCAM and preventing ONL thickness reduction in LED-induced retinal damage rats. In conclusion, while LED light exposure caused retinal damage, treatment with L/Z, QC, and QCG, particularly a combined L/Z and QCG regimen, exhibited protective effects on the retina. This is possibly due to the modulation of neuroplasticity markers and nuclear transcription factors in the rats' retinal cells.

An effective and comprehensible method to detect and evaluate retinal damage due to diabetes complications.

The leading cause of vision loss globally is diabetic retinopathy. Researchers are making great efforts to automatically detect and diagnose correctly diabetic retinopathy. Diabetic retinopathy includes five stages: no diabetic retinopathy, mild diabetic retinopathy, moderate diabetic retinopathy, severe diabetic retinopathy and proliferative diabetic retinopathy. Recent studies have offered several multi-tasking deep learning models to detect and assess the level of diabetic retinopathy. However, the explanation for the assessment of disease severity of these models is limited, and only stops at showing lesions through images. These studies have not explained on what basis the appraisal of disease severity is based. In this article, we present a system for assessing and interpreting the five stages of diabetic retinopathy. The proposed system is built from internal models including a deep learning model that detects lesions and an explanatory model that assesses disease stage. The deep learning model that detects lesions uses the Mask R-CNN deep learning network to specify the location and shape of the lesion and classify the lesion types. This model is a combination of two networks: one used to detect hemorrhagic and exudative lesions, and one used to detect vascular lesions like aneurysm and proliferation. The explanatory model appraises disease severity based on the severity of each type of lesion and the association between types. The severity of the disease will be decided by the model based on the number of lesions, the density and the area of the lesions. The experimental results on real-world datasets show that our proposed method achieves high accuracy of assessing five stages of diabetic retinopathy comparable to existing state-of-the-art methods and is capable of explaining the causes of disease severity.

Fullerol rescues the light-induced retinal damage by modulating Müller glia cell fate.

Excessive light exposure can damage photoreceptors and lead to blindness. Oxidative stress serves a key role in photo-induced retinal damage. Free radical scavengers have been proven to protect against photo-damaged retinal degeneration. Fullerol, a potent antioxidant, has the potential to protect against ultraviolet-B (UVB)-induced cornea injury by activating the endogenous stem cells. However, its effects on cell fate determination of Müller glia (MG) between gliosis and de-differentiation remain unclear. Therefore, we established a MG lineage-tracing mouse model of light-induced retinal damage to examine the therapeutic effects of fullerol. Fullerol exhibited superior protection against light-induced retinal injury compared to glutathione (GSH) and reduced oxidative stress levels, inhibited gliosis by suppressing the TGF-ß pathway, and enhanced the de-differentiation of MG cells. RNA sequencing revealed that transcription candidate pathways, including Nrf2 and Wnt10a pathways, were involved in fullerol-induced neuroprotection. Fullerol-mediated transcriptional changes were validated by qPCR, Western blotting, and immunostaining using mouse retinas and human-derived Müller cell lines MIO-M1 cells, confirming that fullerol possibly modulated the Nrf2, Wnt10a, and TGF-ß pathways in MG, which suppressed gliosis and promoted the de-differentiation of MG in light-induced retinal degeneration, indicating its potential in treating retinal diseases.

Trimethylated chitosan-coated flexible liposomes with resveratrol for topical drug delivery to reduce blue-light-induced retinal damage.

LED-related blue-light-induced damage can cause eye diseases. However, drug delivery in patients with ocular diseases is faced with various challenges. In this study, we developed flexible liposomes based on trimethylated chitosan (TMC-Lipo) to deliver resveratrol for the treatment of retinal diseases. Flexible liposomes can easily cross various biological barriers. Chitosan and its derivatives have adhesive properties and are widely used in mucoadhesive drug delivery systems. Therefore, we wrapped flexible liposomes with trimethylated chitosan via electrostatic adsorption. The charge of the flexible liposomes became positive after encapsulation in TMC, and they remained stable in artificial tears. We assessed the safety of TMC-Lipo in cellular and zebrafish experiments and found that it can be safely used. In addition, treatment with TMC-Lipo significantly reduced H2O2-induced damage to ARPE-19 cells, restored mitochondrial membrane potential, and protected the cells. TMC-Lipo more easily reached the posterior ocular segment of the mice than liposome nanoparticles and attenuated blue-light-induced retinal cytopathy. Our study demonstrates that effective eye drop formulations can be developed based on trimethylated chitosan, which provides a promising approach for the treatment of ocular diseases.

Low-dose rosmarinic acid and thymoquinone accelerate wound healing in retinal pigment epithelial cells.

PURPOSE: Thymoquinone (TQ) and rosmarinic acid (RA) are two biologically active compounds found in plants and that possess remarkable anti-oxidant and anti-inflammatory properties. The present study aimed to investigate the potential protective effects of RA and TQ, which have known anti-inflammatory and anti-oxidant effects, on retinal damage by establishing a wound healing model for retinal pigment epithelial cells (ARPE-19). METHOD: To this end, IC50 doses of RA and TQ in ARPE-19 cells were calculated by MTT assay. Both agents were administered at IC50, IC50/2 and IC50/4 doses for wound healing assay, and wound closure percentages were analyzed. Since the best wound healing was found at IC50/4 dose (low dose) for both agents, other biochemical and molecular analyses were planned to be performed using these doses. Following low dose RA and TQ treatments, the cells were lysed and TGF-ß1 and MMP-9 levels were analyzed by ELISA technique from the cell lysates obtained. In addition, the mRNA expression levels of TLR3, IFN-γ and VEGF were calculated by RT-PCR technique. RESULTS: Low dose of RA and TQ dramatically increased wound healing. RA may have achieved this by increasing levels of MMP-9 and TLR-3. In contrast, the mRNA expression level of VEGF remained unchanged. TQ accelerated wound healing by increasing both the protein levels of TGF-ß1 and MMP-9. Furthermore, low dose of TQ decreased both TLR3 and IFN-γ mRNA expression levels. CONCLUSION: Low doses of RA and TQ were clearly demonstrated to have protective properties against possible damage to retinal pigment epithelial cells.

The cGAS-STING pathway in diabetic retinopathy and age-related macular degeneration.

Diabetic retinopathy and age-related macular degeneration are common retinal diseases with shared pathophysiology, including oxidative stress-induced inflammation. Cellular mechanisms responsible for converting oxidative stress into retinal damage are ill-defined but have begun to clarify. One common outcome of retinal oxidative stress is mitochondrial damage and subsequent release of mitochondrial DNA into the cytosol. This leads to activation of the cGAS-STING pathway, resulting in interferon release and disease-amplifying inflammation. This review summarizes the evolving link between aberrant cGAS-STING signaling and inflammation in common retinal diseases and provides prospective for targeting this system in diabetic retinopathy and age-related macular degeneration. Further defining the roles of this system in the retina is expected to reveal new disease pathology and novel therapeutic approaches.

Low-Intensity Blue Light Exposure Reduces Melanopsin Expression in Intrinsically Photosensitive Retinal Ganglion Cells and Damages Mitochondria in Retinal Ganglion Cells in Wistar Rats.

This study investigated the effect of low-intensity blue light on the albino Wistar rat retina, including intrinsically photosensitive retinal ganglion cells (ipRGCs). Three groups of nine albino Wistar rats were used. One group was continuously exposed to blue light (150 lx) for 2 d (STE); one was exposed to 12 h of blue light and 12 h of darkness for 10 d (LTE); one was maintained in 12 h of white light (150 lx) and 12 h of darkness for 10 d (control). Melanopsin (Opn4) was immunolabelled on retinal whole-mounts. To count and measure Opn4-positive ipRGC somas and dendrites (including Sholl profiles), Neuron J was used. Retinal cryosections were immunolabeled for glial fibrillary acid protein (GFAP) and with terminal deoxynucleotidyl transferase dUTP nick-end labelling for apoptosis detection. LTE reduced the length of Opn4-positive ipRGC dendrites (p = 0.03) and decreased Opn4-immunoreactivity in ipRGC outer stratifying dendrites. LTE and STE decreased the complexity of dendritic arborization (Sholl profile; p < 0.001, p = 0.03, respectively), increased retinal GFAP immunoreactivity (p < 0.001, p = 0.002, respectively), and caused outer segment vesiculation and outer nuclear layer apoptosis. Ultrastructural analysis showed that LTE damaged mitochondria in retinal ganglion cells and in the inner plexiform layer. Thus, LTE to low-intensity blue light harms the retinas of albino Wistar rats.

Identifying new drugs and targets to treat rapidly elevated intraocular pressure for angle closure and secondary glaucomas to curb visual impairment and prevent blindness.

A multitude of pharmacological compounds have been shown to lower and control intraocular pressure (IOP) in numerous species of animals and human subjects after topical ocular dosing or via other routes of administration. Most researchers have been interested in finding drug candidates that exhibit a relatively long duration of action from a chronic therapeutic use perspective, for example to treat ocular hypertension (OHT), primary open-angle glaucoma and even normotensive glaucoma. However, it is equally important to seek and characterize treatment modalities which offer a rapid onset of action to help provide fast relief from quickly rising IOP that occurs in certain eye diseases. These include acute angle-closure glaucoma, primary angle-closure glaucoma, uveitic and inflammatory glaucoma, medication-induced OHT, and other secondary glaucomas induced by eye injury or infection which can cause partial or complete loss of eyesight. Such fast-acting agents can delay or prevent the need for ocular surgery which is often used to lower the dangerously raised IOP. This research survey was therefore directed at identifying agents from the literature that demonstrated ocular hypotensive activity, normalizing and unifying the data, determining their onset of action and rank ordering them on the basis of rapidity of action starting within 30-60 min and lasting up to at least 3-4 h post topical ocular dosing in different animal species. This research revealed a few health authority-approved drugs and some investigational compounds that appear to meet the necessary criteria of fast onset of action coupled with significant efficacy to reduce elevated IOP (by ≥ 20%, preferably by >30%). However, translation of the novel animal-based findings to the human conditions remains to be demonstrated but represent viable targets, especially EP2-receptor agonists (e.g. omidenepag isopropyl; AL-6598; butaprost), mixed activity serotonin/dopamine receptor agonists (e.g. cabergoline), rho kinase inhibitors (e.g. AMA0076, Y39983), CACNA2D1-gene product inhibitors (e.g. pregabalin), melatonin receptor agonists, and certain K+-channel openers (e.g. nicorandil, pinacidil). Other drug candidates and targets were also identified and will be discussed.

Incidence and long-term outcome of laser pointer maculopathy in children.

PURPOSE: Single center study to evaluate the incidence and long-term outcome of laser pointer maculopathy (LPM). METHODS: Medical records of 909,150 patients visiting our institution between 2007 and 2020 were screened in our electronic patient record system using the keywords "laserpointer," "laser pointer," and "solar." RESULTS: Eight patients (6/2 male/female, 11 eyes) with a history of LPM were identified by fundoscopy and optical coherence tomography (OCT), all of whom were children (6/2 male/female). Mean age at injury was 12.1 years (range 6-16). Five children (62.5%) were injured between 2019 and 2020, three (37.5%) between 2007 and 2018. Median best-corrected visual acuity (BCVA) of affected eyes at first presentation was 20/25 (range 20/50-20/16). Follow-up examination was performed in seven children (10 eyes) with a median follow-up period of 18 months (range 0.5-96). BCVA improved in 4 children (5 eyes; BCVA at follow-up 20/22.5, range 20/40-20/16). Three of these four children were treated with oral steroids. OCT revealed acute signs such as intraretinal fluid to resolve quickly, while outer retinal disruption persisted until the last follow-up in eight of eleven eyes. These lesions resembled lesions of patients with solar retinopathy of which seven cases (11 eyes) were identified between 2007 and 2020. CONCLUSION: Readily available consumer laser pointers can damage the retina and the underlying retinal pigment epithelium, possibly leading to long-lasting visual impairments. The number of laser pointer injuries has increased over the last years. Therefore, access to laser pointers for children should be strictly controlled.

Ketorolac and (-)-Epicatechin change retinal GFAP and NRF2 expression on hyperglycemic CD1 mice.

Our objective was to determine whether (-)-Epicatechin administered alone or simultaneously with topical Ketorolac decreased the relative expression of GFAP and modulated the response of Nrf2 in a mouse model with induced hyperglycemia. We found that GFAP and Nrf2 decreased in the groups that received treatments alone or simultaneous during 8 weeks; even when the effect on the Nrf2 was not pronounced, it showed a higher concentration when GFAP decreased. Our results suggest a protective effect of Ketorolac and (-) - Epicatechin, which seem to limit the preclinical retinal damage caused by inflammation in hyperglycemia.