Most irreversible blindness observed with glaucoma and retina-related ocular diseases, including age-related macular degeneration and diabetic retinopathy, have their origin in the posterior segment of the eye, making their physiopathology both complex and interconnected. In addition to the age factor, these diseases share the same mechanism disorder based essentially on oxidative stress. In this context, the imbalance between the production of reactive oxygen species (ROS) mainly by mitochondria and their elimination by protective mechanisms leads to chronic inflammation. Oxidative stress and inflammation share a close pathophysiological process, appearing simultaneously and suggesting a relationship between both mechanisms. The biochemical end point of these two biological alarming systems is the release of different biomarkers that can be used in the diagnosis. Furthermore, oxidative stress, initiating in the vulnerable tissue of the posterior segment, is closely related to mitochondrial dysfunction, apoptosis, autophagy dysfunction, and inflammation, which are involved in each disease progression. In this review, we have analyzed (1) the oxidative stress and inflammatory processes in the back of the eye, (2) the importance of biomarkers, detected in systemic or ocular fluids, for the diagnosis of eye diseases based on recent studies, and (3) the treatment of posterior ocular diseases, based on long-term clinical studies.
The eye is a metabolically active structure, constantly exposed to solar radiations making its structure vulnerable to the high burden of reactive oxygen species (ROS), presenting many molecular interactions. The biomolecular cascade modification is caused especially in diseases of the ocular surface, cornea, conjunctiva, uvea, and lens. In fact, the injury in the anterior segment of the eye takes its origin from the perturbation of the pro-oxidant/antioxidant balance and leads to increased oxidative damage, especially when the first line of antioxidant defence weakens with age. Furthermore, oxidative stress is related to mitochondrial dysfunction, DNA damage, lipid peroxidation, protein modification, apoptosis, and inflammation, which are involved in anterior ocular disease progression such as dry eye, keratoconus, uveitis, and cataract. The different pathologies are interconnected through various mechanisms such as inflammation, oxidative stress making the diagnostics more relevant in early stages. The end point of the molecular pathway is the release of different antioxidant biomarkers offering the potential of predictive diagnostics of the pathology. In this review, we have analysed the oxidative stress and inflammatory processes in the front of the eye to provide a better understanding of the pathomechanism, the importance of biomarkers for the diagnosis of eye diseases, and the recent treatment of anterior ocular diseases.
Glaucoma is a multifactorial neurodegenerative disease and the second leading cause of blindness. Detection of clinically relevant biomarkers would aid better diagnoses and monitoring during treatment. In glaucoma, the protein composition of aqueous humor (AH) is relevant for the discovery of biomarkers. This study analyzes AH protein concentrations of putative biomarkers in patients with primary open-angle glaucoma (POAG) compared to a control group. Biomarkers were selected from known oxidative-stress and inflammatory pathways. Osteopontin (OPN), matrix metalloproteinase 9 (MMP-9), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), and interleukin-10 (IL-10) were measured using the ELISA technique. Thirty-two patients were recruited to the study, including sixteen control and sixteen glaucoma patients. The glaucoma group consisted of patients diagnosed with glaucoma. In both groups, the aqueous humor sample was obtained during cataract surgery. A significant increase in OPN, MMP-9, TNF-alpha, and IL-10 was observed in the POAG aqueous humor, compared to the control group (p < 0.05). Of note, the AH of POAG patients contained 5.6 ± 1.2-fold more OPN compared to that of control patients. Different expression profiles of oxidative stress-related and inflammatory biomarkers were observed between patients with POAG and controls. This confirms the reported involvement of inflammatory and oxidative stress pathways in POAG pathophysiology. In the future, several, targeted AH proteins may be used to generate a potential biomarker expression profile of this disease, aiding diagnoses and disease progression monitoring. This approach highlights the importance of biomarkers in the future. Biomarkers provide a way to measure disease progression and response to treatment. In the future, biomarkers will play a more critical role in the toolkit of ophthalmology healthcare professionals as the field moves towards personalized medicine and precision healthcare.
Purpose: The aim of this study was to develop a new rabbit model of glaucoma produced by GNPs with characteristics like human chronic glaucoma and to evaluate different inflammation and oxidative stress biomarkers related with glaucoma in tears, aqueous humour and retina samples, to characterize the model. Methods: Fifteen rabbits were used to the animal model development, n = 7 for model group, n = 4 for control group and n = 4 for Positive control group. The ocular hypertension model was developed by making multiple intracameral injections of 100 μl of PBS + GNPs(70 nM) in model group, only PBS (10 nM) in the control group and 100 μl of 20% Chondroitin Sulfate in the Positive control group. Increasing intraocular pression (IOP) protocol was developed during a period of 4 weeks by series of two weekly injections, followed by one‐week injection for the model group, to increase the volume of the anterior chamber. IOP was measured by Tonometer for 5 hours postoperatively and daily until the enucleation. Corneal thickness was evaluated by OCT. For biomarkers evaluation, nine rabbits were included, n = 3 for the three group. Tear collection was performed, weekly, using Schirmer test. Following the animal model design, 100 μl of aqueous humour was extracted, weekly, before the intracameral injection for the three groups. After Sacrifice, retina samples were collected. Level of Osteopontin were measured by HPLC, and Level of MMP‐9, TNF‐alpha, TGF‐beta, IL‐8 were measured by Elisa and compared between the groups. Results: The IOP was increased in the study group from 12.7 ± 1.8 mmHg at the baseline to 21.24 ± 5 mmHg after 6 weeks experiments for the model group and to 22.37 ± 4 mmHg for the positive control group, being the trend statistically significant (p < 0.05). The increasing was constant, being around 3 mmHg each week. However, no differences were found in control group for any measurement, keeping in similar values during all experiment. The corneal thickness was increased in the model group (650 ± 300 mm) and positive control group (620 ± 200 mm) comparing to control group (350 ± 50 mm). Therefore, IOP was adjusted, considering the corneal thickness. Regarding biomarkers evaluation, it was found a significant increasing of IL‐8 and MMP‐9 and a decrease of Osteopontin, in tears, after 6 weeks experiments in Model group comparing to Control group. Also, a significant increase of IL‐8 and Osteopontin, in the aqueous humour and in the retina after sacrifice, was found in model group comparing to control group. For TGF‐beta and TNF‐alpha, the difference of the concentration of biomarkers was not significant between the groups. Conclusion: Osteopontin's increase in retina of the model group, comparing to control group, can be a good alternative to convert the ocular hypertension model to Glaucoma model. This model seems to be a great option to study potential biomarkers of glaucoma. New long‐term studies to analyse the effect of GNPs in the ganglion cells density are needed to validate the glaucoma model.
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