The cornea is the anterior transparent surface and the main refracting structure of the eye. Mitochondrial dysfunction and oxidative stress are implicated in the pathogenesis of inherited (e.g. ...Kearns Sayre Syndrome) and acquired corneal diseases (e.g. keratoconus and Fuchs endothelial corneal dystrophy). Both antioxidants and reactive oxygen species are found in the healthy cornea. There is increasing evidence of imbalance in the oxidative balance and mitochondrial function in the cornea in disease states. The cornea is vulnerable to mitochondrial dysfunction and oxidative stress due to its highly exposed position to ultraviolet radiation and high oxygen tension. The corneal endothelium is vulnerable to accumulating mitochondrial DNA (mtDNA) damage due to the post- mitotic nature of endothelial cells, yet their mitochondrial genome is continually replicating and mtDNA mutations can develop and accumulate with age. The unique physiology of the cornea predisposes this structure to oxidative damage, and there is interplay between inherited and acquired mitochondrial dysfunction, oxidative damage and a number of corneal diseases. By targeting mitochondrial dysfunction in corneal disease, emerging treatments may prevent or reduce visual loss.
Glaucoma is a complex neurodegenerative disease of the optic nerve that leads to irreversible sight loss. Lowering intraocular pressure (IOP) medically or surgically represents the mainstay of ...treatment but despite adequate treatment optic nerve function can continue to deteriorate leading to blindness. There is significant clinical and experimental evidence that oxidative stress is involved in the pathogenesis of glaucoma. Decreasing the formation of lipid peroxidation products or scavenging them chemically could be beneficial in limiting the deleterious effects of oxidative stress in glaucoma. A solution to control the susceptibility of PUFAs to noxious lipid peroxidation reactions is by regioselective deuteration. Deuterium incorporated into PUFAs at bis-allylic positions (D-PUFAs) inhibits the rate-limiting step of lipid peroxidation. In this study, we have shown that Tenon’s ocular fibroblasts from glaucoma patients have significantly increased basal oxidative stress compared to non-glaucomatous control patients. Furthermore, we have shown that deuterated polyunsaturated fatty acids (D-PUFAs) provide an enhanced rescue of menadione induced lipid peroxidation in both non-glaucomatous and glaucomatous Tenon’s ocular fibroblasts using malondialdehyde (MDA) levels as a marker. Our study suggests that D-PUFAs may provide a potentially safe and effective method to reduce cytotoxic oxidative stress in glaucoma.
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•Glaucoma is a complex neurodegenerative disease that leads to irreversible sight loss.•Oxidative stress is involved in the pathogenesis of glaucoma.•Oxidative stress was elevated in glaucomatous Tenon's ocular fibroblasts.•Isotopically reinforced D-PUFAs provide protection against lipid peroxidation.
To examine the combined effects of common genetic variants associated with intraocular pressure (IOP) on primary open-angle glaucoma (POAG) phenotype using a polygenic risk score (PRS) ...stratification.
Cross-sectional study.
For the primary analysis, we examined the glaucoma phenotype of 2154 POAG patients enrolled in the Australian and New Zealand Registry of Advanced Glaucoma, including patients recruited from the United Kingdom. For replication, we examined an independent cohort of 624 early POAG patients.
Using IOP genome-wide association study summary statistics, we developed a PRS derived solely from IOP-associated variants and stratified POAG patients into 3 risk tiers. The lowest and highest quintiles of the score were set as the low- and high-risk groups, respectively, and the other quintiles were set as the intermediate risk group.
Clinical glaucoma phenotype including maximum recorded IOP, age at diagnosis, number of family members affected by glaucoma, cup-to-disc ratio, visual field mean deviation, and treatment intensity.
A dose-response relationship was found between the IOP PRS and the maximum recorded IOP, with the high genetic risk group having a higher maximum IOP by 1.7 mmHg (standard deviation SD, 0.62 mmHg) than the low genetic risk group (P = 0.006). Compared with the low genetic risk group, the high genetic risk group had a younger age of diagnosis by 3.7 years (SD, 1.0 years; P < 0.001), more family members affected by 0.46 members (SD, 0.11 members; P < 0.001), and higher rates of incisional surgery (odds ratio, 1.5; 95% confidence interval, 1.1-2.0; P = 0.007). No statistically significant difference was found in mean deviation. We further replicated the maximum IOP, number of family members affected by glaucoma, and treatment intensity (number of medications) results in the early POAG cohort (P ≤ 0.01).
The IOP PRS was correlated positively with maximum IOP, disease severity, need for surgery, and number of affected family members. Genes acting via IOP-mediated pathways, when considered in aggregate, have clinically important and reproducible implications for glaucoma patients and their close family members.
Glaucoma is a progressive optic neuropathy characterized by the neurodegeneration of the retinal ganglion cells (RGCs) resulting in irreversible visual impairment and eventual blindness. RGCs are ...extremely susceptible to mitochondrial compromise due to their marked bioenergetic requirements and morphology. There is increasing interest in therapies targeting mitochondrial health as a method of preventing visual loss in managing glaucoma. The bioenergetic profile of Tenon's ocular fibroblasts from glaucoma patients and controls was investigated using the Seahorse XF24 analyser. Impaired mitochondrial cellular bioenergetics was detected in glaucomatous ocular fibroblasts including basal respiration, maximal respiration and spare capacity. Spare respiratory capacity levels reflect mitochondrial bio-energetic adaptability in response to pathophysiological stress. Basal oxidative stress was elevated in glaucomatous Tenon's ocular fibroblasts and hydrogen peroxide (H2O2) induced reactive oxygen species (ROS) simulated the glaucomatous condition in normal Tenon's ocular fibroblasts. This work supports the role of therapeutic interventions to target oxidative stress or provide mitochondrial energetic support in glaucoma.
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•Mitochondrial bioenergetics were altered in Tenon's ocular fibroblast cells from glaucoma patients.•Impaired mitochondrial cellular bioenergetics was detected in glaucomatous ocular fibroblasts.•Basal oxidative stress was elevated in glaucomatous Tenon's ocular fibroblasts.•This study provides further evidence for the potential of neuroprotective bioenergetic based therapies for glaucoma.
PURPOSE:To evaluate whether the speed of stripping a Descemet membrane endothelial keratoplasty graft influences the graft scroll width.
METHODS:Human corneas suitable for research were selected for ...the study. Pairs of corneas were randomly divided into 2 groups1 cornea was stripped with a slow speed (group 1) and the contralateral with a fast speed (group 2). Slow speed was defined as the total time greater than 150 seconds or speed <0.057 mm/s. Fast peeling was defined as less than 75 seconds or speed >0.11 mm/s. The grafts acquired were evaluated by microscopy for the graft scroll width and endothelial cell density change pre- and post-preparation.
RESULTS:Twenty corneas of 10 donors were included in the analysis. The mean donor age was 68.6 ± 7.58 years. The mean total time of the tissue preparation in group 1 was 282.7 ± 28 seconds and in group 2 was 126 ± 50 seconds (P-value = 0.00000047). The mean speed of stripping in group 1 was 0.045 ± 0.006 mm/s and in group 2 was 0.266 ± 0.093 mm/s (P-value = 0.000027). The graft width in group 1 was 6.4 ± 0.92 mm and in group 2 was 2.87 ± 0.32 mm (P-value = 0.00000014). The mean endothelial cell loss in group 1 was 389 ± 149 cells/mm and in group 2 was 186 ± 63.44 cells/mm (P-value = 0.00134).
CONCLUSION:We found a correlation between the speed of stripping, scroll width, and endothelial cell loss. Slow-peeled Descemet membrane endothelial keratoplasty grafts result in a wider scroll width but were associated with a greater reduction in endothelial cell density.
Purpose: The purpose of this study was to genotype two previously identified SNPs (rs1048661:R141L, and rs3825942:G153D) in the lysyl oxidase-like 1 (LOXL1) gene and determine their association with ...pseudoexfoliation glaucoma (XFG) in patients from Pune, India. Methods: All subjects underwent detailed phenotyping, and DNA extraction was performed on blood samples by using standardized techniques. Exon 1 of the LOXL1 gene containing the SNPs (rs3825942:G153D; rs1048661:R141L) were Sanger sequenced, and the results were analyzed using sequence analysis software SeqScape 2.1.1. Results: Data were analyzed from 71 patients with XFG and 81 disease-negative, age-matched controls. There was a strong association between the G allele of rs3825942 and XFG with an odds ratio of 10.2 (CI: 3.92-26.6; P < 0.001). The G allele of rs1048661 also showed an increase in risk relative to the T allele (OR = 1.49; CI: 0.88-2.51; P = 0.13), but this was not significant. Haplotype combination frequencies were estimated for rs1048661 and rs3825942; the GG haplotype was associated with a significant increase in risk (OR = 3.91; CI: 2.27-6.73; P < 0.001). Both the GA and TG haplotypes were associated with decreased XFG risk, although the latter was not significant (GA: OR = 0.08; CI: 0.03-0.21; P < 0.001; TG: OR = 0.67; CI: 0.40-1.13; P = 0.13). Conclusion: The risk G allele in rs3852942 (G153D) is strongly associated with the development of XFG in the Western Indian population. Genetic screening strategies to identify LOXL1 risk alleles in the population can assist in case definition and early diagnosis, targeting precious resources to high-risk patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The corneal endothelium has a crucial role in maintaining a clear and healthy cornea. Corneal endothelial cell loss occurs naturally with age; however, a diagnosis of glaucoma and surgical ...intervention for glaucoma can exacerbate a decline in cell number and impairment in morphology. In glaucoma, the mechanisms for this are not well understood and this accelerated cell loss can result in corneal decompensation. Given the high prevalence of glaucoma worldwide, this review aims to explore the abnormalities observed in the corneal endothelium in differing glaucoma phenotypes and glaucoma therapies (medical or surgical including with new generation microinvasive glaucoma surgeries). Descemet membrane endothelial keratoplasty (DMEK) is increasingly being used to manage corneal endothelial failure for glaucoma patients and we aim to review the recent literature evaluating the use of this technique in this clinical scenario.
This paper describes a technique for using swept-source anterior segment optical coherence tomography (AS-OCT) to visualize internal bleb microstructure and objectively quantify dimensions of the ...scleral flap and trabeculo-Descemet window (TDW) in non-penetrating glaucoma filtration surgery (GFS). This was a cross-sectional study of 107 filtering blebs of 67 patients who had undergone deep sclerectomy surgery at least 12 months prior. The mean post-operative follow-up duration was 6.5 years +/− 4.1 standard deviation (SD). The maximal bleb height was significantly greater in the complete success (CS) blebs compared to the qualified success (QS) and failed (F) blebs (1.48 vs. 1.17 vs. 1.10 mm in CS vs. QS vs. F, one-way ANOVA, p < 0.0001). In a subcohort of deep sclerectomy blebs augmented by intraoperative Mitomycin-C, the trabeculo-Descemet window was significantly longer in the complete success compared to the qualified success group (613.7 vs. 378.1 vs. 450.8 µm in CS vs. QS vs. F, p = 0.004). The scleral flap length, thickness, and width were otherwise similar across the three outcome groups. The quantification of surgical parameters that influence aqueous outflow in non-penetrating GFS can help surgeons better understand the influence of these structures on aqueous outflow and improve surgical outcomes.
Purpose:
To introduce a new color imaging technique using improved settings of red, green, and blue channels for improved delineation of retinal damage in patients with solar retinopathy.
Method:
A ...retrospective case series of patients with poor vision secondary to solar retinopathy were analyzed. All patients underwent visual acuity, refraction, and dilated fundus examination. A spectral domain–optical coherence tomography of the macula and color fundus imaging using optimized red, green, and blue color setting was performed. Patients were reviewed over a 6-month period. The data were analyzed for statistical significance using an independent t test and a receiver operating characteristic curve.
Results:
In total, 20 eyes of 10 patients were included between 2009 and 2017. The mean age was 24.9 ± 18.1 years. Best corrected visual acuity at first consultation was 0.78 ± 0.11 and after 6 months was 0.83 ± 0.09. Spectral domain–optical coherence tomography demonstrated retinal abnormalities at the myoid zone, ellipsoid zone, and the outer segment of photoreceptors. Receiver operating characteristic curve analysis showed an improving effect (area under the curve = 0.62; 95% confidence interval = 0.42–0.79). The color channels parameters, which improve visualization of the lesions were found to be 67-0.98-255 for the R-guided setting, 19-0.63-121 for the B-guided setting, and 7-1.00-129 for the G-guided setting. The ideal red, green, and blue setting was in 24-0.82-229.
Conclusion:
The use of a new setting of red, green, and blue channels could improve the diagnosis and monitoring of solar retinopathy, hence improving patient care.
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