Photobiomodulation therapy activates YAP and triggers proliferation and dedifferentiation of Müller glia in mammalian retina.

Photobiomodulation therapy has been proposed as a promising therapeutic approach for retinal degenerative diseases. However, its effect on the regenerative capacity in mammalian retina and its intracellular signalling mechanisms remain unknown. Here, we show that photobiomodulation with 670 nm light stimulates Müller glia cell cycle re-entry and dedifferentiation into a progenitor-like state in both the uninjured and injured retina. We also find that 670 nm light treatment inhibits the Hippo pathway, which is activated in Müller glia following NaIO3-induced retinal injury. YAP, a major downstream effector of the Hippo signalling pathway was translocated into the nucleus of Müller glia along with YAP dephosphorylation in retina treated with 670 nm light. Deficiency of YAP attenuated Müller glia cell cycle re-entry and dedifferentiation. Our data reveal that the Hippo-YAP signalling pathway is associated with the photostimulatory effect on regenerative response in mammalian retina, and suggest a potential therapeutic strategy for retinal degenerative diseases. [BMB Reports 2023; 56(9): 502-507].

Ozone treatment for high-dose systemic Steroid-Induced retinal injury.

OBJECTIVE: To investigate the effect of high-dose systemic steroids on retinal tissues and the effectiveness of ozone (O3) therapy. METHODS: Twenty-four New Zealand white rabbits were divided into three groups of eight. Group 1 was accepted as the control group, Group 2 received intramuscular 20 mg/kg methylprednisolone acetate and Group 3 received 14 sessions of ozone treatment in addition to methylprednisolone acetate. The subjects were sacrificed on the 30th day. Retinal tissues were removed. Superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), total antioxidant status (TAS) and total oxidant status (TOS) levels were evaluated for tissue biochemistry and serum ischaemic modified albumin (IMA), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) levels were evaluated with the ELISA method. Haematoxylin-eosin staining and TUNEL evaluation for apoptosis were evaluated as histopathological methods. RESULTS: In the treatment group, antioxidant parameters of TAS, SOD and CAT were higher, oxidative and ischaemic parameters of MDA, TOS and IMA were lower, inflammatory parameters of IL-6 and TNF-α were lower, retinal thickness was better and apoptosis amount was lower. CONCLUSION: Apoptosis increases in retinal tissues due to high dose systemic steroid administration and the retina becomes thinner. With biochemical examination, oxidation parameters increased while antioxidant parameters decreased. Both histopathological and biochemical parameters improved significantly with ozone treatment.

Nieve visual / Visual snow

No disponible

Reactive oxygen species, oxidative stress, glaucoma and hyperbaric oxygen therapy / Especies reactivas de oxígeno, estrés oxidativo, glaucoma y terapia de oxígeno hiperbárico

This review examines the role of oxidative stress in damage to cells of the trabecular meshwork and associated impaired aqueous drainage as well as damage to retinal ganglion cells and associated visual field losses. Consideration is given to the interaction between vascular and mechanical explanations for pathological changes in glaucoma. For example, elevated intraocular pressure (IOP) forces may contribute to ischaemia but there is increasing evidence that altered blood flow in a wider sense is also involved. Both vascular and mechanical theories are involved through fluctuations in intraocular pressure and dysregulation of blood flow. Retinal function is very sensitive to changes in haemoglobin oxygen concentration and the associated variations in the production of reactive oxygen species. Reperfusion injury and production of reactive oxygen species occurs when IOP is elevated or blood pressure is low and beyond the capacity for blood flow autoregulation to maintain appropriate oxygen concentration. Activities such as those associated with postural changes, muscular effort, eye wiping and rubbing which cause IOP fluctuation, may have significant vascular, mechanical, reperfusion and oxidative stress consequences. Hyperbaric oxygen therapy exposes the eye to increased oxygen concentration and the risk of oxidative damage in susceptible individuals. However, oxygen concentration in aqueous humour, and the risk of damage to trabecular meshwork cells may be greater if hyperbaric oxygen is delivered by a hood which exposes the anterior ocular surface to higher than normal oxygen levels. Oronasal mask delivery of hyperbaric oxygen therapy appears to be indicated in these cases (AU)

Esta revisión examina el papel del estrés oxidativo en el daño celular de la red trabecular, la disfunción del drenaje acuoso, así como las lesiones de las células ganglionares de la retina y las pérdidas de campo visual asociadas. Se tiene en cuenta la interacción entre las explicaciones a los cambios patológicos en el glaucoma, desde el punto de vista vascular y mecánico. Por ejemplo, la elevación de las fuerzas de la presión intraocular (PIO) puede contribuir a la isquemia, aunque existe evidencia creciente de que también está implicada la alteración del flujo sanguíneo, en un sentido más amplio. También están implicadas las teorías vasculares y mecánicas a través de las fluctuaciones de la PIO y la desregulación del flujo sanguíneo. La función de la retina es muy sensible a los cambios de la concentración de oxígeno en la hemoglobina y a las variaciones asociadas a la producción de especies reactivas de oxígeno. Las lesiones por reperfusión y la producción de especies reactivas de oxígeno se producen cuando la PIO es elevada o cuando la presión sanguínea es baja, y sobrepasa la capacidad de autoregulación del flujo sanguíneo para mantener la concentración de oxígeno adecuada. Las actividades tales como las asociadas a cambios posturales, esfuerzo muscular, lavado y frotamiento de ojos, que causan fluctuación de la PIO, pueden tener repercusiones considerables de tipo vascular y mecánico, y de reperfusión y estrés oxidativo. La terapia de oxígeno hiperbárico expone al ojo a un incremento de la concentración de oxígeno y al riesgo de daño oxidativo en individuos susceptibles. Sin embargo, la concentración de oxígeno en el humour acuoso y el riesgo de lesiones de las células de la red trabecular pueden ser superiores cuando el oxígeno hiperbárico es liberado por una campana que expone la superficie ocular anterior a unos niveles de oxígeno más elevados de lo normal. La liberación de oxígeno hiperbárico mediante mascarilla oronasal parece más indicada en estos casos (AU)

Mechanisms of Retinal Damage after Ocular Alkali Burns.

Alkali burns to the eye constitute a leading cause of worldwide blindness. In recent case series, corneal transplantation revealed unexpected damage to the retina and optic nerve in chemically burned eyes. We investigated the physical, biochemical, and immunological components of retinal injury after alkali burn and explored a novel neuroprotective regimen suitable for prompt administration in emergency departments. Thus, in vivo pH, oxygen, and oxidation reduction measurements were performed in the anterior and posterior segment of mouse and rabbit eyes using implantable microsensors. Tissue inflammation was assessed by immunohistochemistry and flow cytometry. The experiments confirmed that the retinal damage is not mediated by direct effect of the alkali, which is effectively buffered by the anterior segment. Rather, pH, oxygen, and oxidation reduction changes were restricted to the cornea and the anterior chamber, where they caused profound uveal inflammation and release of proinflammatory cytokines. The latter rapidly diffuse to the posterior segment, triggering retinal damage. Tumor necrosis factor-α was identified as a key proinflammatory mediator of retinal ganglion cell death. Blockade, by either monoclonal antibody or tumor necrosis factor receptor gene knockout, reduced inflammation and retinal ganglion cell loss. Intraocular pressure elevation was not observed in experimental alkali burns. These findings illuminate the mechanism by which alkali burns cause retinal damage and may have importance in designing therapies for retinal protection.

Tyrosine triple mutated AAV2-BDNF gene therapy in a rat model of transient IOP elevation.

PURPOSE: We examined the neuroprotective effects of exogenous brain-derived neurotrophic factor (BDNF), which provides protection to retinal ganglion cells (RGCs) in rodents, in a model of transient intraocular pressure (IOP) elevation using a mutant (triple Y-F) self-complementary adeno-associated virus type 2 vector encoding BDNF (tm-scAAV2-BDNF). METHODS: The tm-scAAV2-BDNF or control vector encoding green fluorescent protein (GFP; tm-scAAV2-GFP) was intravitreally administered to rats, which were then divided into four groups: control, ischemia/reperfusion (I/R) injury only, I/R injury with tm-scAAV2-GFP, and tm-scAAV2-BDNF. I/R injury was then induced by transiently increasing IOP, after which the rats were euthanized to measure the inner retinal thickness and cell counts in the RGC layer. RESULTS: Intravitreous injection of tm-scAAV2-BDNF resulted in high levels of BDNF expression in the neural retina. Histological analysis showed that the inner retinal thickness and cell numbers in the RGC layer were preserved after transient IOP elevation in eyes treated with tm-scAAV2-BDNF but not in the other I/R groups. Significantly reduced glial fibrillary acidic protein (GFAP) immunostaining after I/R injury in the rats that received tm-scAAV2-BDNF indicated reduced retinal stress, and electroretinogram (ERG) analysis confirmed preservation of retinal function in the tm-scAAV2-BDNF group. CONCLUSIONS: These results demonstrate the feasibility and effectiveness of neuroprotective gene therapy using tm-scAAV2-BDNF to protect the inner retina from transiently high intraocular pressure. An in vivo gene therapeutic approach to the clinical management of retinal diseases in conditions such as glaucoma, retinal artery occlusion, hypertensive retinopathy, and diabetic retinopathy thus appears feasible.

Traumatic Branch Retinal Vein Occlusion With Retinal Neovascularization Following Inadvertent Retrobulbar Needle Perforation.

Retrobulbar injection of anesthesia is one of the most common procedures performed for ophthalmic surgery. Complications are rare but can be potentially serious, including retrobulbar hemorrhage, brainstem anesthesia, and inadvertent globe perforation. This is the preliminary report describing branch retinal vein occlusion (BRVO) secondary to accidental retrobulbar needle laceration with subsequent preretinal neovascularization.

Protective Effect of Fucoxanthin Isolated from Laminaria japonica against Visible Light-Induced Retinal Damage Both in Vitro and in Vivo.

With increasingly serious eye exposure to light stresses, such as light-emitting diodes, computers, and widescreen mobile phones, efficient natural compounds for preventing visible light-induced retinal damages are becoming compelling needs in the modern society. Fucoxanthin, as the main light absorption system in marine algae, may possess an outstanding bioactivity in vision protection because of its filtration of blue light and excellent antioxidative activity. In this work, both in vitro and in vivo simulated visible light-induced retinal damage models were employed. The in vitro results revealed that fucoxanthin exhibited better bioactivities than lutein, zeaxanthin, and blueberry anthocyanins in inhibiting overexpression of vascular endothelial growth factor, resisting senescence, improving phagocytic function, and clearing intracellular reactive oxygen species in retinal pigment epithelium cells. The in vivo experiment also confirmed the superiority of fucoxanthin than lutein in protecting retina against photoinduced damage. This excellent bioactivity may be attributed to its unique structural features, including allenic, epoxide, and acetyl groups. Fucoxanthin is expected to be an important ocular nutrient in the future.

Salidroside protects retinal endothelial cells against hydrogen peroxide-induced injury via modulating oxidative status and apoptosis.

Oxidative stress can cause injury in retinal endothelial cells. Salidroside is a strong antioxidative and cytoprotective supplement in Chinese traditional medicine. In this study, we investigated the effects of salidroside on H2O2-induced primary retinal endothelial cells injury. Salidroside decreased H2O2-induced cell death, and efficiently suppressed cellular ROS production, malondialdehyde generation, and cell apoptosis induced by H2O2 treatment. Salidroside induced the intracellular mRNA expression, protein expression, and enzymatic activities of catalase and Mn-SOD and increased the ratio of Bcl2/Bax. Our results demonstrated that salidroside protected retinal endothelial cells against oxidative injury through increasing the Bcl2/Bax signaling pathway and activation of endogenous antioxidant enzymes. This finding presents salidroside as an attractive agent with potential to attenuate retinopathic diseases.

Protective effects of Radix Pseudostellariae extract against retinal laser injury.

BACKGROUND: This study aimed to analyze the protective effects of a saponin extract from Radix Pseudostellariae (RP) on retinal laser injury based on a retinal photocoagulation model. METHODS: Fifty-eight rabbits were randomly divided into three groups: Group A (saponin extract orally), Group B (physiological saline), and Group C (control). The animals were sacrificed 1 day, 7 days, 14 days, and 30 days after photocoagulation and lesions were evaluated with fundus photography, light microscopy, and electron microscopy. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured, and expression levels of c-fos and Bax genes were also determined. RESULTS: The lesion sizes in Group A were smaller than in Group B. The levels of SOD in Group B were significantly lower than in groups A and C (P<0.001) at all time points. The MDA levels were significantly lower than in groups B and C (P<0.001) at the 1 month point, while the apoptosis rate of Group A was significantly lower than that of Group B at all time points. The expression levels of the c-fos gene in Group B were significantly higher than that in groups A and C, and expression levels of the Bax gene in Group A were significantly lower than that in groups B and C. CONCLUSION: The saponin extract of RP can inhibit oxidative stress, downregulate the levels of c-fos and Bax gene expression, and inhibit apoptosis in the retina after photocoagulation.

Protective effect of light emitting diode phototherapy on fluorescent light induced retinal damage in Wistar strain albino rats.

BACKGROUND: Artificial light at night alters retinal physiology. Several studies have shown that light emitting diode phototherapy protects the retina from the damaging effects of acute light exposure. OBJECTIVE: The aim of this study has been to elucidate the protective effects of 670 nm LED light on retinal damage induced by chronic fluorescent light in Wistar rats. METHODS: Male Wistar albino rats were divided into four groups: group 1 were control (CL), group 2, 3 and 4 were exposed to fluorescent light (FL), LED preexposure+fluorescent light exposure (LL) and only LED light exposure (OL) respectively. All animals were maintained in their specific exposure regime for 30 days. Fluorescent light of 1800 lx was exposed between 8 pm to 8 am. Rats were exposed to therapeutic LED light of 670 nm of 9 J/cm2 at 25 mW/cm2 for 6 min duration. Histopathological changes in the retina were studied. RESULTS: Animals of the FL group showed a significant reduction in the outer nuclear layer thickness and cell count in addition to the total thickness of the retina. LL group which were exposed to 670 nm LED prior to exposure to fluorescent light showed a significant decrease in the degree of damage. CONCLUSIONS: 670 nm LED light preexposure is protective to retinal cells against fluorescent light-induced damage.

Management of retinal detachment in block related globe perforation with pneumatic retinopexy.

Retinal detachment after ocular perforation related to local anesthesia is a common complication, which is usually associated with a poor prognosis despite complex vitreoretinal surgical procedures. We report a case of 62-year-old male with cataract surgery done 4 weeks back with nasal retinal detachment with a posterior break. Pneumatic retinopexy was performed and laser barrage of the breaks was done the next day when the retina got attached. A vision of 20/30 was achieved at the end of 2 months. To the best of our knowledge, this is a first case report in literature where pneumatic retinopexy was used to manage a retinal detachment caused by block-related perforation.

Experimental measure of retinal impact force resulting from intraocular foreign body dropped onto retina through media of differing viscosity.

BACKGROUND: To evaluate and compare the perfluorocarbon liquid, silicone oil, and viscoelastic against standard saline, in their ability to dampen the impact force of a foreign body, dropped within the eye. In an experimental surgical model in where cohesive and adhesive forces of the substances are not enough to float heavy-than-water foreign bodies. METHODS: A model of ophthalmic surgery was constructed. A BB pellet was dropped from 24 mm onto a force transducer through four different fluids: balanced salt solution, perfluoro-n-octane, viscoelastic, and silicone oil. The impact energy (force) for each case was measured and recorded by the force transducer. The mean force of impact for each fluid was compared using the Student t-test. RESULTS: Silicone oil resulted in the lowest force of impact. Both silicone oil and viscoelastic dampened the impact an order of magnitude more than perfluoro-n-octane and balanced salt solution. CONCLUSIONS: Silicone oil and viscoelastic cushioned the force from a dropped BB. They may be useful adjuncts to prevent iatrogenic retinal injury during vitrectomy for intraocular foreign body removal.