Abstract
Purpose: To investigate the association of autophagy-related gene expression with age-related macular degeneration (AMD). Methods: Patients with AMD were recruited for analysis by conjunctival impression cytology. mRNA was assessed by real-time polymerase chain reaction (RT-PCR) to evaluate whether the expression of 26 autophagy-related genes (ATGs) was correlated with AMD. Further studies on cell viability and autophagic flux in response to oxidative stress by H2O2 were performed in human retinal pigment epithelial (RPE) cell lines based on the results of impression cytology. Results: Both the neovascular AMD (nAMD) and polypoidal choroidal vasculopathy (PCV) groups had significantly higher mRNA levels of gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1) and microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) than the control group, but there was no significant difference between these two groups. Age difference existed only in the AMD group. GABARAPL1 and MAP1LC3B mRNA expression increased significantly after acute oxidative stress in adult retinal pigment epithelial (ARPE-19) cells. Cell viability significantly increased and decreased in the cells harboring GABARAPL1 expression vector and silenced with siRNA against GABARAPL1, respectively, during short-term oxidative stress, whereas viability increased in the GABARAPL1-silenced cells after long-term oxidative stress. Silencing GABARAPL1 itself caused a reduction in autophagic flux under both short and long-term oxidative stress. Conclusion: Our study showed the possibility of assessing autophagy-related gene expression by conjunctival impression cytology. GABARAPL1 was significantly higher in AMD. Although an in vitro study showed an initial protective effect of autophagy, a cell viability study revealed the possibility of a harmful effect after long-term oxidative injury. The underlying mechanism or critical factors require further investigation.
Highlights
Advanced age-related macular degeneration (AMD) is a common cause of uncorrectable severe vision loss in elderly people worldwide [1,2,3]
Degeneration of retinal pigment epithelial (RPE) cells has been implicated in the early pathogenesis of AMD, the vision changes result from photoreceptor death in the central retina [6,7]
To examine if autophagy-related (ATG) gene expression is associated with patients with AMD and polypoidal choroidal vasculopathy (PCV), the cells obtained by impression cytology were stained to observe cellular morphology (Figure 1A)
Summary
Advanced age-related macular degeneration (AMD) is a common cause of uncorrectable severe vision loss in elderly people worldwide [1,2,3]. Recent studies in the genetics, imaging and clinical response to treatment suggested differences in pathophysiology between PCV and typical nAMD [4]. While the pathophysiology remains poorly understood, a growing body of evidence indicates that cumulative oxidative stress is related to the underlying mechanism of AMD [5]. Degeneration of retinal pigment epithelial (RPE) cells has been implicated in the early pathogenesis of AMD, the vision changes result from photoreceptor death in the central retina [6,7]. It has been demonstrated that these cells die through apoptosis in the eyes of AMD patients [8,9]
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