Proteomic Profiling Revealed Mitochondrial Dysfunction in Photoreceptor Cells under Hyperglycemia

Diabetic retinopathy (DR) was identified as a leading cause of blindness and vision impairment in 2020. In addition to vasculopathy, DR has been found to involve retinal neurons, including amacrine cells and retinal ganglion cells. Despite possessing features that are susceptible to diabetic conditi...

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Main Authors: Christie Hang-I Lam, Jimmy Ka-Wai Cheung, Dennis Yan-Yin Tse, Thomas Chuen Lam
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/21/13366
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author Christie Hang-I Lam
Jimmy Ka-Wai Cheung
Dennis Yan-Yin Tse
Thomas Chuen Lam
author_facet Christie Hang-I Lam
Jimmy Ka-Wai Cheung
Dennis Yan-Yin Tse
Thomas Chuen Lam
author_sort Christie Hang-I Lam
collection DOAJ
description Diabetic retinopathy (DR) was identified as a leading cause of blindness and vision impairment in 2020. In addition to vasculopathy, DR has been found to involve retinal neurons, including amacrine cells and retinal ganglion cells. Despite possessing features that are susceptible to diabetic conditions, photoreceptor cells have received relatively little attention with respect to the development of DR. Until recently, studies have suggested that photoreceptors secret proinflammatory molecules and produce reactive oxygen species that contribute to the development of DR. However, the effect of hyperglycemia on photoreceptors and its underlying mechanism remains elusive. In this study, the direct effect of high glucose on photoreceptor cells was investigated using a 661w photoreceptor-like cell line. A data-independent sequential window acquisition of all theoretical mass spectra (SWATH)-based proteomic approach was employed to study changes induced by high glucose in the proteomic profile of the cells. The results indicated that high glucose induced a significant increase in apoptosis and ROS levels in the 661w cells, with mitochondrial dysfunction among the major affected canonical pathways. The involvement of mitochondrial dysfunction was further supported by increased mitochondrial fission and reduced mitochondrial bioenergetics. Collectively, these findings provide a biological basis for a possible role of photoreceptors in the pathogenesis of DR.
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spelling doaj.art-c43aadee361041e2aac7d651884d433b2023-11-24T05:06:48ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123211336610.3390/ijms232113366Proteomic Profiling Revealed Mitochondrial Dysfunction in Photoreceptor Cells under HyperglycemiaChristie Hang-I Lam0Jimmy Ka-Wai Cheung1Dennis Yan-Yin Tse2Thomas Chuen Lam3School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong KongSchool of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong KongSchool of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong KongSchool of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong KongDiabetic retinopathy (DR) was identified as a leading cause of blindness and vision impairment in 2020. In addition to vasculopathy, DR has been found to involve retinal neurons, including amacrine cells and retinal ganglion cells. Despite possessing features that are susceptible to diabetic conditions, photoreceptor cells have received relatively little attention with respect to the development of DR. Until recently, studies have suggested that photoreceptors secret proinflammatory molecules and produce reactive oxygen species that contribute to the development of DR. However, the effect of hyperglycemia on photoreceptors and its underlying mechanism remains elusive. In this study, the direct effect of high glucose on photoreceptor cells was investigated using a 661w photoreceptor-like cell line. A data-independent sequential window acquisition of all theoretical mass spectra (SWATH)-based proteomic approach was employed to study changes induced by high glucose in the proteomic profile of the cells. The results indicated that high glucose induced a significant increase in apoptosis and ROS levels in the 661w cells, with mitochondrial dysfunction among the major affected canonical pathways. The involvement of mitochondrial dysfunction was further supported by increased mitochondrial fission and reduced mitochondrial bioenergetics. Collectively, these findings provide a biological basis for a possible role of photoreceptors in the pathogenesis of DR.https://www.mdpi.com/1422-0067/23/21/13366diabetic retinopathySWATH-MSmitochondrial dysfunction
spellingShingle Christie Hang-I Lam
Jimmy Ka-Wai Cheung
Dennis Yan-Yin Tse
Thomas Chuen Lam
Proteomic Profiling Revealed Mitochondrial Dysfunction in Photoreceptor Cells under Hyperglycemia
International Journal of Molecular Sciences
diabetic retinopathy
SWATH-MS
mitochondrial dysfunction
title Proteomic Profiling Revealed Mitochondrial Dysfunction in Photoreceptor Cells under Hyperglycemia
title_full Proteomic Profiling Revealed Mitochondrial Dysfunction in Photoreceptor Cells under Hyperglycemia
title_fullStr Proteomic Profiling Revealed Mitochondrial Dysfunction in Photoreceptor Cells under Hyperglycemia
title_full_unstemmed Proteomic Profiling Revealed Mitochondrial Dysfunction in Photoreceptor Cells under Hyperglycemia
title_short Proteomic Profiling Revealed Mitochondrial Dysfunction in Photoreceptor Cells under Hyperglycemia
title_sort proteomic profiling revealed mitochondrial dysfunction in photoreceptor cells under hyperglycemia
topic diabetic retinopathy
SWATH-MS
mitochondrial dysfunction
url https://www.mdpi.com/1422-0067/23/21/13366
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AT jimmykawaicheung proteomicprofilingrevealedmitochondrialdysfunctioninphotoreceptorcellsunderhyperglycemia
AT dennisyanyintse proteomicprofilingrevealedmitochondrialdysfunctioninphotoreceptorcellsunderhyperglycemia
AT thomaschuenlam proteomicprofilingrevealedmitochondrialdysfunctioninphotoreceptorcellsunderhyperglycemia