RESUMO
Glaucoma, a leading cause of blindness worldwide, encompasses a group of pathological conditions affecting the optic nerve and is characterized by progressive retinal ganglion cell loss, cupping of the optic nerve head, and distinct visual field defects. While elevated intraocular pressure (IOP) is the main risk factor for glaucoma, many patients do not have elevated IOP. Consequently, other risk factors, such as ocular blood flow abnormalities and immunological factors, have been implicated in its pathophysiology. Traditional therapeutic strategies primarily aim to reduce IOP, but there is growing interest in developing novel treatment approaches to improve disease management and reduce the high rates of severe visual impairment. In this context, targeting the ocular renin-angiotensin-aldosterone system (RAAS) has been found as a potential curative strategy. The RAAS contributes to glaucoma development through key effectors such as prorenin, angiotensin II, and aldosterone. Recent evidence has highlighted the potential of using RAAS modulators to combat glaucoma, yielding encouraging results. Our study aims to explore the molecular pathways linking the ocular RAAS and glaucoma, summarizing recent advances that elucidate the role of the RAAS in triggering oxidative stress, inflammation, and remodelling in the pathogenesis of glaucoma. Additionally, we will present emerging therapeutic approaches that utilize RAAS modulators and antioxidants to slow the progression of glaucoma.
RESUMO
Purpose: In Germany, approximately one-third of the harvested donor corneas are not suitable for transplantation, mostly due to insufficient endothelial cell density (ECD). The ECD can only be reliably determined after harvesting and processing of the cornea. Our group has previously developed a predictive model for corneal ECD: \( {Predicted\, ECD} = 2919-6^{\ast}\;{age}\; [{years}]-189\; [{if\, male}]\\ -7^{\ast}\;{death-to-explantation\, interval\,} [{hours}]\\ - 378\; [{if\, pseudophakic}] \;{cells/mm}^2 \). Methods: A total of 2.999 consecutive donor corneas harvested between 2017 and 2021 from the Eye Bank of Rhineland-Palatinate in Mainz, Germany, were included. An actual ECD of >2000 cells/mm2 was defined as the cutoff value. To evaluate the clinical utility of the prognostic model as a screening instrument for transplant eligibility in an independent cohort, we performed a decision curve analysis. Results: The median predicted ECD was 2061 cells/mm2 (interquartile range [IQR] = 1834 to 2221), whereas the median actual ECD was 2377 cells/mm2 (IQR = 1907 to 2624). There was a positive correlation between predicted and actual ECD (correlation coefficient = 0.411; P < 0.01). Our predictive model for ECD is a strong predictor for an actual ECD greater than 2000 (odds ratio = 1.374, 95% confidence interval [CI]) per 100 cells; P < 0.001, area under the curve [AUC] of 0.73). Decision curve analysis showed that the predictive model yielded a positive net benefit in clinical settings. Conclusions: Decision curve analysis demonstrated a positive net benefit of the ECD predictive model in clinical settings with limited eye bank resources. Translational Relevance: In possible scenarios where a choice between corneal grafts is required, or in countries with limited eye bank infrastructure and staff, the initial estimate of ECD from the formula may be beneficial.
Assuntos
Transplante de Córnea , Endotélio Corneano , Bancos de Olhos , Doadores de Tecidos , Humanos , Contagem de Células , Masculino , Endotélio Corneano/citologia , Endotélio Corneano/transplante , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Idoso de 80 Anos ou mais , Alemanha , Seleção do Doador , Estudos RetrospectivosRESUMO
Nitric oxide synthases (NOS) are essential regulators of vascular function, and their role in ocular blood vessels is of paramount importance for maintaining ocular homeostasis. Three isoforms of NOS-endothelial (eNOS), neuronal (nNOS), and inducible (iNOS)-contribute to nitric oxide production in ocular tissues, exerting multifaceted effects on vascular tone, blood flow, and overall ocular homeostasis. Endothelial NOS, primarily located in endothelial cells, is pivotal for mediating vasodilation and regulating blood flow. Neuronal NOS, abundantly found in nerve terminals, contributes to neurotransmitter release and vascular tone modulation in the ocular microvasculature. Inducible NOS, expressed under inflammatory conditions, plays a role in response to pathological stimuli. Understanding the distinctive contributions of these NOS isoforms in retinal blood vessels is vital to unravel the mechanisms underlying various ocular diseases, such diabetic retinopathy. This article delves into the unique contributions of NOS isoforms within the complex vascular network of the retina, elucidating their significance as potential therapeutic targets for addressing pathological conditions.
Assuntos
Óxido Nítrico Sintase , Vasos Retinianos , Humanos , Vasos Retinianos/metabolismo , Vasos Retinianos/fisiopatologia , Animais , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico/metabolismo , Retinopatia Diabética/fisiopatologia , Retinopatia Diabética/enzimologia , Retinopatia Diabética/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismoRESUMO
PURPOSE: To investigate whether trabecular aspiration (TA) has an effective medium-term intraocular pressure (IOP)-lowering and medication-saving effect in patients with pseudoexfoliation glaucoma (PEG). In addition, a subgroup analysis of patients with or without a previous trabeculectomy was performed. METHODS: Records of 290 consecutive eyes with PEG that underwent TA between 2006 and 2012 at the Department of Ophthalmology, Mainz, Germany, were retrospectively analyzed with a follow-up period of 3 years. The main outcomes were IOP and the need for further medical treatment. RESULTS: Of the 290 eyes with PEG that received TA, 167 eyes from 127 patients met the inclusion criteria. Among these eyes, 128 received TA and cataract surgery (Phaco-TA) without having had a trabeculectomy (group I) before, 29 had Phaco-TA after a previous trabeculectomy (group II) and 10 underwent stand-alone TA after a previous trabeculectomy (group III). In the whole cohort, the median IOP decreased immediately after TA and remained significantly lower compared to the baseline throughout the period of 36 months. Likewise, the median number of antiglaucoma drugs was reduced over the whole period. At the same time, in group I, the median IOP and the number of antiglaucoma drugs were reduced over 36 months. In contrast, in the post-trabeculectomy groups (group II and III), the median IOP and the number of antiglaucoma drugs could not be reduced. While most of the patients that received Phaco-TA with or without a previous trabeculectomy (group I and II) did not require further surgical intervention during the follow-up period, almost all patients receiving stand-alone TA after a previous trabeculectomy (group III) needed surgical therapy, most of them between the second and the third year following TA. CONCLUSIONS: Phaco-TA has an effective medium-term pressure-lowering and medication-saving effect, especially in patients without a previous trabeculectomy. In trabeculectomized eyes, the effect of TA is limited but still large enough to delay more invasive surgical interventions in some patients.
RESUMO
Diabetic retinopathy (DR) represents a severe complication of diabetes mellitus, characterized by irreversible visual impairment resulting from microvascular abnormalities. Since the global prevalence of diabetes continues to escalate, DR has emerged as a prominent area of research interest. The development and progression of DR encompass a complex interplay of pathological and physiological mechanisms, such as high glucose-induced oxidative stress, immune responses, vascular endothelial dysfunction, as well as damage to retinal neurons. Recent years have unveiled the involvement of genomic and epigenetic factors in the formation of DR mechanisms. At present, extensive research explores the potential of biomarkers such as cytokines, molecular and cell therapies, antioxidant interventions, and gene therapy for DR treatment. Notably, certain drugs, such as anti-VEGF agents, antioxidants, inhibitors of inflammatory responses, and protein kinase C (PKC)-ß inhibitors, have demonstrated promising outcomes in clinical trials. Within this context, this review article aims to introduce the recent molecular research on DR and highlight the current progress in the field, with a particular focus on the emerging and experimental treatment strategies targeting the immune and redox signaling pathways.
RESUMO
Acknowledged as a significant pathogenetic driver for numerous diseases, aging has become a focal point in addressing the profound changes associated with increasing human life expectancy, posing a critical concern for global public health. Emerging evidence suggests that factors influencing vascular aging extend their impact to choroidal and retinal blood vessels. The objective of this work is to provide a comprehensive overview of the impact of vascular aging on ocular blood vessels and related diseases. Additionally, this study aims to illuminate molecular insights contributing to vascular cell aging, with a particular emphasis on the choroid and retina. Moreover, innovative molecular targets operating within the domain of ocular vascular aging are presented and discussed.
RESUMO
Thyroid eye disease (TED) is an autoimmune condition affecting the orbit and the eye with its adnexa, often occurring as an extrathyroidal complication of Graves' disease (GD). Orbital inflammatory infiltration and the stimulation of orbital fibroblasts, triggering de novo adipogenesis, an overproduction of hyaluronan, myofibroblast differentiation, and eventual tissue fibrosis are hallmarks of the disease. Notably, several redox signaling pathways have been shown to intensify inflammation and to promote adipogenesis, myofibroblast differentiation, and fibrogenesis by upregulating potent cytokines, such as interleukin (IL)-1ß, IL-6, and transforming growth factor (TGF)-ß. While existing treatment options can manage symptoms and potentially halt disease progression, they come with drawbacks such as relapses, side effects, and chronic adverse effects on the optic nerve. Currently, several studies shed light on the pathogenetic contributions of emerging factors within immunological cascades and chronic oxidative stress. This review article provides an overview on the latest advancements in understanding the pathophysiology of TED, with a special focus of the interplay between oxidative stress, immunological mechanisms and environmental factors. Furthermore, cutting-edge therapeutic approaches targeting redox mechanisms will be presented and discussed.
Assuntos
Oftalmopatia de Graves , Oxirredução , Estresse Oxidativo , Humanos , Oftalmopatia de Graves/imunologia , Oftalmopatia de Graves/metabolismo , Oftalmopatia de Graves/terapia , Estresse Oxidativo/imunologia , Animais , Citocinas/metabolismo , Citocinas/imunologia , Transdução de Sinais/imunologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismoRESUMO
BACKGROUND: Peripheral hypertrophic subepithelial corneal opacification (PHSCO) is a corneal disease that may severely affect vision. The major goal of this study was to test the hypothesis that tear secretion, medication and systemic diseases are associated with PHSCO. METHODS: This is a retrospective, case-control study conducted at the Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz. We analysed medical records of patients diagnosed with PHSCO. Sex, age, Schirmer's test II, general medication and medical history were assessed and compared to an age- and sex-matched control group from the Gutenberg Health Study (GHS). RESULTS: One hundred ninety-five eyes of 112 patients with PHSCO were included. Eighty-eight patients were female with a mean age of 55.3 ± 14.7 years (23-89 years) and 24 patients were male with a mean age of 59.3 ± 12.6 years (38-84 years). In 83 patients (74.1%) both eyes were involved. The Schirmer's test II was significantly reduced in patients with PHSCO compared to the GHS control group (p < 0.001). Patients with PHSCO were more frequently administered artificial tears and steroid eye drops (p < 0.001) and were more hyperopic than healthy controls (p = 0.01). Systemic diseases or medication did not differ markedly between PHSCO and healthy controls. CONCLUSION: Reduced tear secretion and more frequent use of artificial tears in patients with PHSCO suggest a link between PHSCO and dry eye disease. The results of the study do not support our hypothesis that PHSCO is associated with systemic diseases. Interestingly, patients with PHSCO were less frequently on ß-blockers than control subjects.
Assuntos
Opacidade da Córnea , Lágrimas , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Adulto , Lágrimas/metabolismo , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Adulto Jovem , Opacidade da Córnea/diagnóstico , Opacidade da Córnea/fisiopatologia , Opacidade da Córnea/metabolismo , Epitélio Corneano/metabolismo , Epitélio Corneano/patologia , Epitélio Corneano/efeitos dos fármacos , Hipertrofia , Lubrificantes Oftálmicos/administração & dosagemRESUMO
Retinopathy of prematurity (ROP) is a proliferative vascular ailment affecting the retina. It is the main risk factor for visual impairment and blindness in infants and young children worldwide. If left undiagnosed and untreated, it can progress to retinal detachment and severe visual impairment. Geographical variations in ROP epidemiology have emerged over recent decades, attributable to differing levels of care provided to preterm infants across countries and regions. Our understanding of the causes of ROP, screening, diagnosis, treatment, and associated risk factors continues to advance. This review article aims to present the pathophysiological mechanisms of ROP, including its treatment. Specifically, it delves into the latest cutting-edge treatment approaches targeting hypoxia and redox signaling pathways for this condition.
RESUMO
Age-related macular degeneration (AMD) is a prevalent degenerative disorder of the central retina, which holds global significance as the fourth leading cause of blindness. The condition is characterized by a multifaceted pathophysiology that involves aging, oxidative stress, inflammation, vascular dysfunction, and complement activation. The complex interplay of these factors contributes to the initiation and progression of AMD. Current treatments primarily address choroidal neovascularization (CNV) in neovascular AMD. However, the approval of novel drug therapies for the atrophic and more gradual variant, known as geographic atrophy (GA), has recently occurred. In light of the substantial impact of AMD on affected individuals' quality of life and the strain it places on healthcare systems, there is a pressing need for innovative medications. This paper aims to provide an updated and comprehensive overview of advancements in our understanding of the etiopathogenesis of AMD. Special attention will be given to the influence of aging and altered redox status on mitochondrial dynamics, cell death pathways, and the intricate interplay between oxidative stress and the complement system, specifically in the context of GA. Additionally, this review will shed light on newly approved therapies and explore emerging alternative treatment strategies in the field. The objective is to contribute to the ongoing dialogue surrounding AMD, offering insights into the latest developments that may pave the way for more effective management and intervention approaches.
RESUMO
Diabetes mellitus, the most prevalent endocrine disorder, not only impacts the retina but also significantly involves the ocular surface. Diabetes contributes to the development of dry eye disease and induces morphological and functional corneal alterations, particularly affecting nerves and epithelial cells. These changes manifest as epithelial defects, reduced sensitivity, and delayed wound healing, collectively encapsulated in the context of diabetic keratopathy. In advanced stages of this condition, the progression to corneal ulcers and scarring further unfolds, eventually leading to corneal opacities. This critical complication hampers vision and carries the potential for irreversible visual loss. The primary objective of this review article is to offer a comprehensive overview of the pathomechanisms underlying diabetic keratopathy. Emphasis is placed on exploring the redox molecular pathways responsible for the aberrant structural changes observed in the cornea and tear film during diabetes. Additionally, we provide insights into the latest experimental findings concerning potential treatments targeting oxidative stress. This endeavor aims to enhance our understanding of the intricate interplay between diabetes and ocular complications, offering valuable perspectives for future therapeutic interventions.