Dataset Information

Retinal Aging Transcriptome and Cellular Landscape in Association With the Progression of Age-Related Macular Degeneration.

ABSTRACT:

Purpose

Age is the main risk factor for age-related macular degeneration (AMD), a leading cause of blindness in the elderly, with limited therapeutic options.

Methods

Here, we analyze the transcriptomic characteristics and cellular landscape of the aging retinas from controls and patients with AMD.

Results

We identify the aging genes in the neural retina, which are associated with innate immune response and inflammation. Deconvolution analysis reveals that the estimated proportions of M2 macrophages are significantly increased with both age and AMD severity. Moreover, we find that proportions of Müller glia are significantly increased only with age but not with AMD severity. Several genes associated with both age and AMD severity, particularly C1s and MR1, are strong positively correlated with the proportions of Müller glia.

Conclusions

Our studies expand the genetic and cellular landscape of AMD and provide avenues for further studies on the relationship between age and AMD.

SUBMITTER: Wang JH

PROVIDER: S-EPMC10148661 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

Retinal Aging Transcriptome and Cellular Landscape in Association With the Progression of Age-Related Macular Degeneration.

Wang Jiang-Hui JH Wong Raymond C B RCB Liu Guei-Sheung GS

Investigative ophthalmology & visual science 20230401 4

<h4>Purpose</h4>Age is the main risk factor for age-related macular degeneration (AMD), a leading cause of blindness in the elderly, with limited therapeutic options.<h4>Methods</h4>Here, we analyze the transcriptomic characteristics and cellular landscape of the aging retinas from controls and patients with AMD.<h4>Results</h4>We identify the aging genes in the neural retina, which are associated with innate immune response and inflammation. Deconvolution analysis reveals that the estimated pro ...[more]

PMID: 37099020

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Project description:Age-related macular degeneration (AMD), the leading cause of blindness in elderly populations, involves the loss of central vision due to progressive dysfunction of the retinal pigment epithelium (RPE) and subsequent loss of light-sensing photoreceptors. While age is a key risk factor, not every aged individual develops AMD. Thus, the critical question is what specific cellular changes tip the balance from healthy aging to disease. To distinguish between changes associated with aging and AMD, we compared the RPE proteome in human eye bank tissue from nondiseased donors during aging (n = 50, 29-91 years) and in donors with AMD (n = 36) compared to age-matched donors without disease (n = 28). Proteins from RPE cells were separated on two-dimensional gels, analyzed for content, and identified using mass spectrometry. A total of 58 proteins displayed significantly altered content with either aging or AMD. Proteins involved in metabolism, protein turnover, stress response, and cell death were altered with both aging and AMD. However, the direction of change was predominantly opposite. With aging, we detected an overall decrease in metabolism and reductions in stress-associated proteins, proteases, and chaperones. With AMD, we observed upregulation of metabolic proteins involved in glycolysis, TCA, and fatty acid metabolism, with a concurrent decline in oxidative phosphorylation, suggesting a reprogramming of energy utilization. Additionally, we detected upregulation of proteins involved in the stress response and protein turnover. Predicted upstream regulators also showed divergent results, with inhibition of inflammation and immune response with aging and activation of these processes with AMD. Our results support the idea that AMD is not simply advanced aging but rather the culmination of perturbed protein homeostasis, defective bioenergetics, and increased oxidative stress within the aging RPE, exacerbated by environmental factors and the genetic background of an individual.

Dataset Information

Retinal Aging Transcriptome and Cellular Landscape in Association With the Progression of Age-Related Macular Degeneration.

Purpose

Methods

Results

Conclusions

Publications

Retinal Aging Transcriptome and Cellular Landscape in Association With the Progression of Age-Related Macular Degeneration.

Similar Datasets

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