Search Results (30)

The prevalence of hypoxia-caused eye diseases is increasing, but effective, non-invasive treatment options are not available. Abscisic acid (ABA) is a plant hormone with anti-inflammatory and antioxidant effects. ABA is also present in various mammalian tissues and plays an important role in metabolic processes. Therefore, we aimed to investigate the potential protective role of ABA eye drops in ischemic retinopathy. Retinal ischemia was induced by permanent unilateral common carotid artery occlusion (UCCAO) in mice. Half of the animals received ABA eye drops two times a day for two weeks. Optical coherence tomography (OCT) was used to follow the changes in retinal thickness. Moreover, immunohistochemistry and molecular biology methods were used to explore the morphological changes and the underlying mechanisms, respectively. Based on OCT measurements, ischemic retinopathy was successfully developed. The decrease in the thickness of numerous retinal layers could be prevented with ABA eye drops. The ganglion cell number decreased significantly after UCCAO in the central and peripheral regions of the retina. ABA treatment could moderate the damage in both regions. Furthermore, our apoptosis array results suggest that ABA regulates the apoptotic pathways under hypoxic conditions. In conclusion, ABA eye drops may represent a new potential therapeutic option for the treatment of ischemic retinopathy. Full article

The continuously growing diabetes population is a significant concern with type 2 diabetic retinal disease (T2DRD), which is a leading cause of permanent blindness. However, the underlying pathophysiological mechanism of T2DRD has not yet been fully understood. Pituitary adenylate cyclase-activating polypeptide (PACAP) was first isolated from the ovine hypothalamus based on its stimulating effect on the adenylate cyclase enzyme in anterior pituitary cells. PACAP38 (PACAP with 38 amino acids) activates anti-apoptotic pathways, inhibits pro-apoptotic signaling, and creates an anti-inflammatory environment in the retina. The aim of the present study was to test the possible retinoprotective effect of the topical administration of PACAP38 in a type 2 diabetic animal model induced by a high-fat diet and the intraperitoneally injected low-dose streptozotocin (STZ). Wistar rats were divided into four groups: the control, control + PACAP38, diabetes, and diabetes + PACAP38 groups randomly. Type 2 diabetes was induced with the combination of STZ (30 mg/kg) and a high-fat diet. All rats were treated topically two times a day for 16 weeks: the control + PACAP38 and diabetes + PACAP38 groups were applied with PACAP38 eye drops (1 µg/drop), while the control and diabetes groups were administered using vehicles (artificial tears). The diabetes model was validated by a fasting oral glucose tolerance test (OGTT) and C-peptide ELISA test. Animals were monitored during the whole experiment for the progression of the disease using electroretinography (ERG) and optical coherence tomography (OCT). Post-mortem immunohistochemistry and a vessel analysis were performed in the retina samples after 16 weeks. An OGTT, a C-peptide ELISA test, and the investigation of blood parameters proved the development of type 2 diabetes. Significant differences could be detected in visual function between the two diabetic groups at week 16 (in the a-wave, b-wave, and OP amplitudes), where the diabetes PACAP38-treated group was similar to the control ones. OCT measurements correlated with ERG data, where the total retinal thickness was preserved in the diabetes + PACAP38 group. PACAP38 also protected the microvascular structure in the retina. Topically administered PACAP38 has potent neuroprotective effects against type 2 diabetic retinal disease; therefore, it could be a promising therapeutic approach for the treatment of T2DRD. Full article

Background: Retinitis pigmentosa (RP), the leading cause of inherited blindness in adults, is marked by the progressive degeneration of rod photoreceptors in the retina. While gene therapy has shown promise in treating RP in patients with specific mutations, no effective therapies currently exist for the majority of patients with diverse genetic backgrounds. Additionally, no intervention can yet prevent or delay photoreceptor loss across the broader RP patient population. Resveratrol (RES), a naturally occurring polyphenol, has shown cytoprotective effects in various neurodegenerative disease models; however, its therapeutic potential is limited by low bioavailability. Methods: In this study, we synthesized novel RES derivatives and assessed their retinoprotective effects in a murine model of RP (rd10 mice). Results: Among these derivatives, piceid octanoate (PIC-OCT) significantly delayed photoreceptor degeneration in the RP model, demonstrating superior efficacy compared to RES. Conclusions: PIC-OCT shows strong potential as a leading candidate for developing new therapeutic strategies for RP. Full article

Retinal ischemia–reperfusion (I/R) injury is a critical pathogenic mechanism in various eye diseases, and an effective therapeutic strategy remains unresolved. Natural derivatives have recently reemerged; therefore, in our present study, we examined the potential therapeutic effects of a stilbenoid that is chemically related to resveratrol. Pterostilbene, recognized for its anti-inflammatory, anti-carcinogenic, anti-diabetic, and neuroprotective properties, counteracts oxidative stress during I/R injury through various mechanisms. This study explored pterostilbene as a retinoprotective agent. Male Sprague Dawley rats underwent retinal I/R injury and one-week reperfusion and were treated with either vehicle or pterostilbene. After this functional electroretinographical (ERG) measurement, Western blot and histological analyses were performed. Pterostilbene treatment significantly improved retinal function, as evidenced by increased b-wave amplitude on ERG. Histological studies showed reduced retinal thinning and preserved the retinal structure in the pterostilbene-treated groups. Moreover, Western blot analysis revealed a decreased expression of glial fibrillary acidic protein (GFAP) and heat shock protein 70 (HSP70), indicating reduced glial activation and cellular stress. Additionally, the expression of pro-apoptotic and inflammatory markers, poly(ADP-ribose) polymerase 1 (PARP1) and nuclear factor kappa B (NFκB) was significantly reduced in the pterostilbene-treated group. These findings suggest that pterostilbene offers protective effects on the retina by diminishing oxidative stress, inflammation, and apoptosis, thus preserving retinal function and structure following I/R injury. This study underscores pterostilbene’s potential as a neuroprotective therapeutic agent for treating retinal ischemic injury and related disorders. Full article

Sea buckthorn (Hippophae rhamnoides L.) is a tree or shrub with small, orange berries. Sea buckthorn seeds have shown many properties beneficial to human health, including antioxidant, anti-hypertensive, anti-hyperlipidemic, and retinoprotective activities. Seeds, as a component of food, are often exposed to high temperatures, which can increase or decrease their biological activity. In our previous study, we showed that both raw and roasted sea buckthorn seeds had significant antioxidant activity, which was measured in human plasma in vitro. In this paper, we evaluated the effect of extracts from raw and roasted sea buckthorn seeds on several parameters of hemostasis in vitro, including thrombus formation in full blood (measured by the Total Thrombus formation Analysis System—T-TAS), blood platelet activation (based on the exposition of P-selectin, the active form of GPIIb/IIIa on their surface and platelet-derived microparticles formation), aggregation (measured with impedance aggregometry), adhesion to fibrinogen and collagen, arachidonic acid metabolism in washed platelets stimulated by thrombin, and COX-1 activity. We also measured the levels of free 8-isoprostane in plasma and the total non-enzymatic antioxidant status of plasma. The extract from roasted seeds (50 µg/mL) significantly prolonged the time of occlusion measured by T-TAS—the AUC₁₀ (area under the curve) value was decreased by approximately 18%. Both extracts decreased the exposition of the active form of GPIIb/IIIa on the surface of platelets activated with 10 μM ADP (by 38.4–62.2%) and 20 μM ADP (by 39.7–51.3%). Moreover, the extract from raw seeds decreased the exposition of P-selectin on the surface of platelets stimulated with 20 μM ADP (by 31.2–34.9%). The adhesion of thrombin-stimulated platelets to fibrinogen and collagen was inhibited only by the extract from roasted sea buckthorn seeds (by 20–30%). Moreover, the extract from raw seeds inhibited the level of TBARS (thiobarbituric acid-reactive substances, an indicator of enzymatic peroxidation of arachidonic acid) in washed platelets stimulated with thrombin; the activity of COX-1 was inhibited by both extracts, although the effect of the extract from raw seeds was stronger. These results indicate that sea buckthorn seeds have anti-platelet activity that is not decreased by thermal processing, but more research is needed to determine which exact chemical compounds and mechanisms are responsible for this phenomenon. Full article

Retinal vascular diseases and consequential metabolic disturbances in the eye are major concerns for healthcare systems all around the world. BGP-15, a drug candidate small-molecule [O-(3-piperidino-2-hydroxy-1-propyl) nicotinic amidoxime dihydrochloride], has been formerly demonstrated by our workgroup to be retinoprotective both in the short and long term. Based on these results, the present study was performed to investigate the efficacy of BGP in an eyedrop formulation containing sulfobutylether-β-cyclodextrin (SBECD), which is a solubility enhancer as well. Electroretinographical evaluations were carried out and BGP was demonstrated to improve both scotopic and photopic retinal a- and b-waves, shorten their implicit times and restore oscillatory potentials after ischemia–reperfusion. It was also observed to counteract retinal thinning after ischemia–reperfusion in the eyes of Sprague Dawley rats. This small-molecule drug candidate is able to compensate for experimental global eye ischemia–reperfusion injury elicited by ligation of blood vessels in rats. We successfully demonstrated that BGP is able to exert its protective effects on the retina even if administered in the form of eyedrops. Full article

Glaucoma is characterized by cupping of the optic disc, apoptotic degeneration of retinal ganglion cells (RGCs) and their axons, and thinning of the retinal nerve fiber layer, with patchy loss of vision. Elevated intraocular pressure (IOP) is a major risk factor for hypertensive glaucoma and the only modifiable one. There is a need to find novel compounds that counteract other risk factors contributing to RGC degeneration. The oil derived from the wild olive tree (Olea europaea var. sylvestris), also called Acebuche (ACE), shows powerful anti-inflammatory, antioxidant and retinoprotective effects. We evaluated whether ACE oil could counteract glaucoma-related detrimental effects. To this aim, we fed mice either a regular or an ACE oil-enriched diet and then induced IOP elevation through intraocular injection of methylcellulose. An ACE oil-enriched diet suppressed glaucoma-dependent retinal glia reactivity and inflammation. The redox status of the glaucomatous retinas was restored to a control-like situation, and ischemia was alleviated by an ACE oil-enriched diet. Notably, retinal apoptosis was suppressed in the glaucomatous animals fed ACE oil. Furthermore, as shown by electroretinogram analyses, RGC electrophysiological functions were almost completely preserved by the ACE oil-enriched diet. These ameliorative effects were IOP-independent and might depend on ACE oil’s peculiar composition. Although additional studies are needed, nutritional supplementation with ACE oil might represent an adjuvant in the management of glaucoma. Full article

Despite the high probability of glaucoma-related blindness, its cause is not fully understood and there is no efficient therapeutic strategy for neuroprotection. Vascular factors have been suggested to play an important role in glaucoma development and progression. Previously, we have proven the neuroprotective effects of pituitary adenylate-cyclase-activating polypeptide (PACAP) eye drops in an inducible, microbeads model in rats that is able to reproduce many clinically relevant features of human glaucoma. In the present study, we examined the potential protective effects of PACAP1-38 on the retinal vasculature and the molecular changes in hypoxia. Ocular hypertension was induced by injection of microbeads into the anterior chamber, while control rats received PBS. PACAP dissolved in vehicle (1 µg/drop) or vehicle treatment was started one day after the injections for four weeks three times a day. Retinal degeneration was assessed with optical coherence tomography (OCT), and vascular and molecular changes were assessed by immunofluorescence labeling. HIF1-α and VEGF-A protein levels were measured by Western blot. OCT images proved severe retinal degeneration in the glaucomatous group, while PACAP1-38 eye drops had a retinoprotective effect. Vascular parameters were deteriorated and molecular analysis suggested hypoxic conditions in glaucoma. PACAP treatment exerted a positive effect against these alterations. In summary, PACAP could prevent the severe damage to the retina and its vasculature induced by ocular hypertension in a microbeads model. Full article

Aucubin is an iridoid glycoside widely spread in the families Cornaceae, Garryaceae, Orobanchaceae, Globulariaceae, Eucommiaceae, Scrophulariaceae, Plantaginaceae, and Rubiaceae. This review is intended to provide data on the physicochemical characteristics, isolation methods, and biological activities of aucubin and its producing plants. Aucubin is unstable and can be deglycosylated into its aglycone, aucubigenin. Various chromatographic methods (column chromatography, vacuum liquid chromatography, medium pressure liquid chromatography, and high-performance liquid chromatography) have been used together to isolate aucubin, mainly with the stationary phase C-18 and the mobile phase water–methanol solution made in gradients. In vitro and in vivo studies reveal that aucubin has a wide range of activities, including anti-inflammatory, antioxidant, anxiolytic and antidepressant, antidiabetic, antifibrotic, antimicrobial, anticancer, antihyperlipidemic, gastroprotective, cardioprotective, hepatoprotective, retinoprotective, neuroprotective, osteoprotective, and renoprotective. Even though aucubin has been extensively investigated, further research in humans is urgently needed primarily to substantiate the clinical evidence. Moreover, extensive studies on its drug delivery systems will help maximize efficacy and minimize side effects. Full article

An imbalance of homeostasis in the retina leads to neuron loss and this eventually results in a deterioration of vision. If the stress threshold is exceeded, different protective/survival mechanisms are activated. Numerous key molecular actors contribute to prevalent metabolically induced retinal diseases—the three major challenges are age-related alterations, diabetic retinopathy and glaucoma. These diseases have complex dysregulation of glucose-, lipid-, amino acid or purine metabolism. In this review, we summarize current knowledge on possible ways of preventing or circumventing retinal degeneration by available methods. We intend to provide a unified background, common prevention and treatment rationale for these disorders and identify the mechanisms through which these actions protect the retina. We suggest a role for herbal medicines, internal neuroprotective substances and synthetic drugs targeting four processes: parainflammation and/or glial cell activation, ischemia and related reactive oxygen species and vascular endothelial growth factor accumulation, apoptosis and/or autophagy of nerve cells and an elevation of ocular perfusion pressure and/or intraocular pressure. We conclude that in order to achieve substantial preventive or therapeutic effects, at least two of the mentioned pathways should be targeted synergistically. A repositioning of some drugs is considered to use them for the cure of the other related conditions. Full article

Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment worldwide. The development of AMD is associated with inflammation, oxidative stress, and progressive proteostasis imbalance, in the regulation of which c-Jun N-terminal kinases (JNK) play a crucial role. JNK inhibition is discussed as an alternative way for prevention and treatment of AMD and other neurodegenerative diseases. Here we assess the retinoprotective potential of the recently synthesized JNK inhibitor 11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt (IQ-1S) using senescence-accelerated OXYS rats as a model of AMD. The treatment with IQ-1S (50 mg/kg body weight intragastric) during the period of active disease development (from 4.5 to 6 months of age) improved some (but not all) histological abnormalities associated with retinopathy. IQ-1S improved blood circulation, increased the functional activity of the retinal pigment epithelium, reduced the VEGF expression in the endothelial cells, and increased the expression of PEDF in the neuroretina. The result was a decrease in the degeneration of photoreceptors and neurons of the inner layers. IQ-1S significantly improved the retinal ultrastructure and increased the number of mitochondria, which were significantly reduced in the neuroretina of OXYS rats compared to Wistar rats. It seems probable that using IQ-1S can be a good prophylactic strategy to treat AMD. Full article

Diabetic retinopathy (DR) is the most frequent microvascular complication of diabetes mellitus (DM), estimated to affect approximately one-third of the diabetic population, and the most common cause of preventable vision loss. The available treatment options focus on the late stages of this complication, while in the early stages there is no dedicated treatment besides optimizing blood pressure, lipid and glycemic control; DR is still lacking effective preventive methods. glucagon-like peptide 1 receptor agonists (GLP-1 Ras) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors have a proven effect in reducing risk factors of DR and numerous experimental and animal studies have strongly established its retinoprotective potential. Both drug groups have the evident potential to become a new therapeutic option for the prevention and treatment of diabetic retinopathy and there is an urgent need for further comprehensive clinical trials to verify whether these findings are translatable to humans. Full article

Ommochromes are pigments of invertebrates that exhibit oxidative stress protection. The aim of this study was to investigate ommochromes extracted from cephalopod’s skin for their ability to inhibit age-related-macular degeneration (AMD)-related factors such as H₂O₂-induced and iron-dependent oxidative stress (ferroptosis and erastin), accumulation of advanced glycation end-products (AGEs), as well as vascular endothelial growth factor (VEGF), and inflammatory cytokines (interleukin 6 and interleukin 8) secretion. As cell systems, we used primary porcine retinal pigment epithelium (RPE), human retinal pigment epithelium cell line ARPE-19 and uveal melanoma cell line OMM-1. In vitro, ommochromes produced an antiglycation effect by the inhibition of fructosylation reaction. The ommochromes showed protective effects against erastin- induced cell death in ARPE-19. In addition, in long-term stimulation (7 days) ommochromes decreased constitutively secreted VEGF, as well as interleukin 6 and interleukin 8 induced by Poly I:C in primary RPE. No relevant effects were detected in OMM-1 cells. The effects are dependent on the cell system, time of exposition, and concentration. This substance is of interest for further research concerning age-related macular degeneration. Full article

The retinal pigment epithelium (RPE) expresses the Serpinf1 gene to produce pigment epithelium-derived factor (PEDF), a retinoprotective protein that is downregulated with cell senescence, aging and retinal degenerations. We determined the expression of senescence-associated genes in the RPE of 3-month-old mice that lack the Serpinf1 gene and found that Serpinf1 deletion induced H2ax for histone H2AX protein, Cdkn1a for p21 protein, and Glb1 gene for β-galactosidase. Senescence-associated β-galactosidase activity increased in the Serpinf1 null RPE when compared with wild-type RPE. We evaluated the subcellular morphology of the RPE and found that ablation of Serpinf1 increased the volume of the nuclei and the nucleoli number of RPE cells, implying chromatin reorganization. Given that the RPE phagocytic function declines with aging, we assessed the expression of the Pnpla2 gene, which is required for the degradation of photoreceptor outer segments by the RPE. We found that both the Pnpla2 gene and its protein PEDF-R declined with the Serpinf1 gene ablation. Moreover, we determined the levels of phagocytosed rhodopsin and lipids in the RPE of the Serpinf1 null mice. The RPE of the Serpinf1 null mice accumulated rhodopsin and lipids compared to littermate controls, implying an association of PEDF deficiency with RPE phagocytosis dysfunction. Our findings establish PEDF loss as a cause of senescence-like changes in the RPE, highlighting PEDF as both a retinoprotective and a regulatory protein of aging-like changes associated with defective degradation of the photoreceptor outer segment in the RPE. Full article

Ischemic eye diseases are major causes of vision impairment. Thus, potential retinoprotective effects of N’N-dimethyltryptamine (DMT) were investigated. To inhibit its rapid breakdown by monoamine-oxidase A (MAO-A) enzyme, DMT was co-administered with harmaline, a β-carboline in the Amazonian Ayahuasca brew. Using ligation, 60 min of ischemia was provoked in eyes of rats, followed by 7 days of reperfusion whilst animals received harmaline alone, DMT + harmaline, or vehicle treatment. After 1 week of reperfusion, electroretinographical (ERG) measurements, histological analysis, and Western blot were performed. Harmaline alone exhibited retinoprotection in ischemia–reperfusion (I/R) which was, surprisingly, counterbalanced by DMT in case of co-administration. As both MAO-A inhibition and DMT increase serotoninergic tone synergistically, communicated to be anti-ischemic, thus, involvement of other pathways was investigated. Based on our experiments, DMT and harmaline exert opposite effects on important ocular proteins such as PARP1, NFκB, MMP9, or HSP70, each having a critical role in a different mechanism of eye-ischemia-related pathologies, e.g., cell death, inflammation, tissue destruction, and oxidative stress. Since DMT is proclaimed to be a promising drug candidate, its potentially undesirable effect on eye-ischemia should be further investigated. Meanwhile, this experiment revealed the potential therapeutic effect of MAO-A inhibitor harmaline in I/R-related eye diseases. Full article