Abstract

Age-related macular degeneration (AMD) is an eye disease that impairs the sharp and central vision need for daily activities. Recent advances in molecular biology research not only lead to a better understanding of the genetics and pathophysiology of AMD but also to the development of applications based on targeted gene expressions to treat the disease. Clarification of molecular pathways that causing to development and progression in dry and wet types of AMD needs comprehensive and comparative investigations in particular precious biopsies involving peripheral blood samples from the patients. Therefore, in this investigation, dry and wet types of AMD patients and healthy individuals were aimed at investigating in regard to targeted gene candidates by using gene expression analysis for the first time. 13 most potent candidate genes involved in neurodegeneration were selected via in silico approach and investigated through gene expression analysis to suggest new targets for disease therapy. For the analyses, 30 individuals (10 dry and 10 wet types AMD patients and 10 healthy people) were involved in the study. SYBR-Green based Real-Time PCR analysis was performed on isolated peripheral blood mononuclear cells (PBMCs) to analyze differentially expressed genes related to these cases. According to the investigations, only the CRP gene was found to be upregulated for both dry and wet disease types. When the downregulated genes were analyzed, it was found that 11 genes were commonly decreased for both dry and wet types in the aspect of expression pattern. From these genes, CFH, CX3CR1, FLT1, and TIMP3 were found to have the most downregulated gene expression properties for both diseases. From these results, it might be concluded that these common upregulated and downregulated genes could be used as targets for early diagnosis and treatment for AMD.

Highlights

  • Age-related macular degeneration (AMD) is a clinical condition that affects individuals aged 50 years and over and causes a progressive decrease in visual acuity by progressing with pigmentary and atrophic changes in the macula [1]

  • It was found that the CX3CR1, FLT1, IGFBP3, MAPK3, SOD1, STAT3, VGEFA, tissue inhibitor of metalloproteinases 3 (TIMP3), and SERPING1 gene expressions were decreased in both Dry-AMD and Wet-AMD patients

  • FLT1 and TIMP3 genes were investigated as the highest downregulated common genes for Dry-AMD and Wet-AMD

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Summary

Introduction

Age-related macular degeneration (AMD) is a clinical condition that affects individuals aged 50 years and over and causes a progressive decrease in visual acuity by progressing with pigmentary and atrophic changes in the macula [1]. A neurodegenerative disease affecting the photoreceptor, retinal pigment epithelium (RPE), Bruch’s membrane, and choriocapillaris in the macula is considered as the AMD disease. It is the most common cause of vision loss in people aged 65 and over in developed countries. The exudative neovascular form is the wet type that results in central vision loss due to choroidal neovascularization directed to the subretinal macular region and the fastest progressing form of AMD. Drusen was previously defined only as lipofuscin accumulation, microscopic examinations performed with different immunohistochemistry dyes found that it contains lipids, carbohydrates, and proteins such as amyloid, fibronectin, vitronectin, and complement factors [4]

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