The Role of Oxidative Stress and the Importance of miRNAs as Potential Biomarkers in the Development of Age-Related Macular Degeneration

Malgorzata Mrowicka,Ewa Kucharska,Barbara Smigielska,Jacek Pawel Szaflik,Jerzy Szaflik,Ireneusz Majsterek,Jerzy Mrowicki

doi:10.3390/pr9081328

Abstract

Age-related macular degeneration (AMD) is the primary cause of blindness in developed countries. With the progressive aging of the population, AMD is a significant ophthalmological problem in the population over 50 years of age. The etiology of AMD is known to be based on various biochemical, immunological and molecular pathways and to be influenced by a range of genetic and environmental elements. This review provides an overview of the pathophysiological role of oxidative stress and free radicals in the retina with a special focus on the DNA repair efficiency and enzymatic antioxidant defense. It also presents a correlation between miRNA profile and AMD, and indicates their involvement in inflammation, angiogenesis, increased oxidation of cellular components, enzymatic antioxidant capacity and DNA repair efficiency, which play particularly important roles in AMD pathogenesis. Gene silencing by miRNAs can induce changes in antioxidant enzymes, leading to a complex interplay between redox imbalance by free radicals and miRNAs in modulating cellular redox homeostasis.

Highlights

Age-related macular degeneration (AMD) is a progressive, neurodegenerative disease that affects the macula of the retina
The pigmentary abnormalities in the retinal pigment epithelium (RPE), drusen and Bruch’s membrane, and the molecular changes associated with this disease, are believed to be caused by inflammation, angiogenesis, and increased oxidation of cellular components, which play a central role in the pathogenesis and progression of AMD [2]
Let-7 family members are known to be pro-angiogenic. These findings strongly indicate that increased Let-7 expression in serum may reflect neovascularization in AMD patients

Summary

Introduction

Age-related macular degeneration (AMD) is a progressive, neurodegenerative disease that affects the macula of the retina. AMD is a disease affecting four components of the visual organ: photoreceptors, retinal pigment epithelium (RPE), Bruch’s membrane, and choroidal capillaries. This process results in the destabilization of four key physiological functions: homeostasis/stress response, extracellular remodeling, complement-related inflammation, and phagocytosis. The pigmentary abnormalities in the RPE, drusen and Bruch’s membrane, and the molecular changes associated with this disease, are believed to be caused by inflammation, angiogenesis, and increased oxidation of cellular components, which play a central role in the pathogenesis and progression of AMD [2]. The resulting overproduction of free radicals, is thought to be a major factor affecting RPE in the pathophysiology of AMD. Some researchers have reported that mRNA transcription factors are sensitive to redox status [6,7]

AMD—Risk Factors

AMD—Enzymatic Antioxidant Capacity

AMD—DNA Damage and Repair

AMD—miRNA Expression and Diagnostic Markers

Findings

Conclusions