Involvement of autophagic pathway in the progression of retinal degeneration in a mouse model of diabetes

71Citations
Citations of this article
51Readers
Mendeley users who have this article in their library.

Abstract

The notion that diabetic retinopathy (DR) is essentially a micro-vascular disease has been recently challenged by studies reporting that vascular changes are preceded by signs of damage and loss of retinal neurons. As to the mode by which neuronal death occurs, the evidence that apoptosis is the main cause of neuronal loss is far from compelling. The objective of this study was to investigate these controversies in a mouse model of streptozotocin (STZ) induced diabetes. Starting from 8 weeks after diabetes induction there was loss of rod but not of cone photoreceptors, together with reduced thickness of the outer and inner synaptic layers. Correspondingly, rhodopsin expression was downregulated and the scotopic electroretinogram (ERG) is suppressed. In contrast, cone opsin expression and photopic ERG response were not affected. Suppression of the scotopic ERG preceded morphological changes as well as any detectable sign of vascular alteration. Only sparse apoptotic figures were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and glia was not activated. The physiological autophagy flow was altered instead, as seen by increased LC3 immunostaining at the level of outer plexiform layer (OPL) and upregulation of the autophagic proteins Beclin-1 and Atg5. Collectively, our results show that the streptozotocin induced DR in mouse initiates with a functional loss of the rod visual pathway. The pathogenic pathways leading to cell death develop with the initial dysregulation of autophagy well before the appearance of signs of vascular damage and without strong involvement of apoptosis.

References Powered by Scopus

Fiji: An open-source platform for biological-image analysis

43360Citations
N/AReaders
Get full text

A guided tour into subcellular colocalization analysis in light microscopy

3968Citations
N/AReaders
Get full text

Diabetic retinopathy

2612Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Diabetic retinopathy pathogenesis and the ameliorating effects of melatonin; involvement of autophagy, inflammation and oxidative stress

242Citations
N/AReaders
Get full text

Autophagy and inflammasomes

169Citations
N/AReaders
Get full text

The neurovascular unit and the pathophysiologic basis of diabetic retinopathy

150Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Piano, I., Novelli, E., Della Santina, L., Strettoi, E., Cervetto, L., & Gargini, C. (2016). Involvement of autophagic pathway in the progression of retinal degeneration in a mouse model of diabetes. Frontiers in Cellular Neuroscience, 10(FEB). https://doi.org/10.3389/fncel.2016.00042

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 17

55%

Researcher 10

32%

Professor / Associate Prof. 3

10%

Lecturer / Post doc 1

3%

Readers' Discipline

Tooltip

Neuroscience 10

38%

Medicine and Dentistry 7

27%

Agricultural and Biological Sciences 5

19%

Biochemistry, Genetics and Molecular Bi... 4

15%

Save time finding and organizing research with Mendeley

Sign up for free