Abstract
To discover the mechanisms underlying the progression of diabetic retinopathy (DR), a more comprehensive understanding of the biomolecular processes in individual retinal cells subjected to hyperglycemia is required. Despite extensive studies, the changes in the biochemistry of retinal layers during the development of DR are not well known. In this study, we aimed to determine a more detailed understanding of the natural history of DR in Akita/+ (type 1 diabetes model) male mice with different duration of diabetes. Employing label-free spatially resolved Fourier transform infrared (FT-IR) chemical imaging engaged with multivariate analysis enabled us to identify temporal-dependent reproducible biomarkers of the individual retinal layers from mice with 6 weeks,12 weeks, 6 months, and 10 months of age. We report, for the first time, the nature of the biochemical alterations over time in the biochemistry of distinctive retinal layers namely photoreceptor retinal layer (PRL), inner nuclear layer (INL), and plexiform layers (OPL, IPL). Moreover, we present the molecular factors associated with the changes in the protein structure and cellular lipids of retinal layers induced by different duration of diabetes. Our paradigm provides a new conceptual framework for a better understanding of the temporal cellular changes underlying the progression of DR.
Highlights
Diabetic retinopathy (DR) is a progressive retinal neurovascular dysfunction that can lead to blindness[1]
We highlighted the bio-molecular changes of retinal layers, and their potential contribution to pathogenesis of diabetic retinopathy (DR), with different duration of diabetes
Precise temporal biomarkers of oxidative stress in the retina with sub-cellular spatial resolution level were obtained and the specific macromolecular functional groups associated with the damage were delineated
Summary
Diabetic retinopathy (DR) is a progressive retinal neurovascular dysfunction that can lead to blindness[1]. The various cellular components of the retina, especially the vascular cells, are susceptible to the hyperglycemic environment that triggers unique biochemical and cellular alterations These cellular changes occur through a number of pathways including, elevated oxidative stress[2], protein kinase C (PKC) activation[3,4], and advanced glycation end (AGE) product formation[5]. Depth of penetration in the eye, contrast from imaging modalities, optical sectioning, and the incapability of early intervention, are some restraints that hindered an in-depth understanding of the pathogenesis of DR in microscopic realm[15] Overcoming these technical limitations would facilitate a better understanding of the natural history of DR. We report the biochemical changes in the individual layers of retina from Akita/+ mice, as a function of the progression of diabetes
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