Evaluation of the Efficacy of Intravitreal and Subtenon-Administered Mesenchymal Stem Cell-Derived Exosomes in an Experimental Diabetic Retinopathy Model

Project no. 31864 · Status: Kapanmış (Yayın bekleniyor) · 2023

Summary

<p>Diabetic&nbsp;retinopathy&nbsp;(DR)&nbsp;is&nbsp;a&nbsp;type&nbsp;of&nbsp;microangiopathy&nbsp;resulting&nbsp;from&nbsp;the&nbsp;chronic&nbsp;effects&nbsp;of&nbsp;diabetes.&nbsp;In&nbsp;its&nbsp;pathogenesis,&nbsp;the&nbsp;inhibition&nbsp;of&nbsp;inflammatory&nbsp;processes&nbsp;and&nbsp;neurovascular&nbsp;damage&nbsp;is&nbsp;of&nbsp;critical&nbsp;importance.&nbsp;This&nbsp;study&nbsp;aims&nbsp;to&nbsp;present&nbsp;an&nbsp;innovative&nbsp;therapeutic&nbsp;approach&nbsp;for&nbsp;DR&nbsp;treatment&nbsp;by&nbsp;utilising&nbsp;the&nbsp;immunomodulatory&nbsp;and&nbsp;regenerative&nbsp;potential&nbsp;of&nbsp;mesenchymal&nbsp;stem&nbsp;cell-derived&nbsp;exosomes&nbsp;(MSC-Exo).&nbsp;The&nbsp;original&nbsp;aspect&nbsp;of&nbsp;our&nbsp;project&nbsp;is&nbsp;the&nbsp;comparative&nbsp;evaluation&nbsp;of&nbsp;subtenon&nbsp;injection,&nbsp;which&nbsp;is&nbsp;critical&nbsp;in&nbsp;terms&nbsp;of&nbsp;clinical&nbsp;application&nbsp;safety&nbsp;and&nbsp;low&nbsp;complication&nbsp;rates,&nbsp;with&nbsp;traditional&nbsp;intravitreal&nbsp;application.</p><p>In&nbsp;our&nbsp;study,&nbsp;rats&nbsp;with&nbsp;blood&nbsp;glucose&nbsp;levels&nbsp;of&nbsp;16.7&nbsp;mmol/L&nbsp;or&nbsp;higher&nbsp;following&nbsp;a&nbsp;single&nbsp;dose&nbsp;of&nbsp;streptozotocin&nbsp;(STZ)&nbsp;were&nbsp;considered&nbsp;diabetic.&nbsp;In&nbsp;Sprague&nbsp;Dawley&nbsp;rats&nbsp;with&nbsp;induced&nbsp;diabetes,&nbsp;the&nbsp;development&nbsp;of&nbsp;DR&nbsp;was&nbsp;confirmed&nbsp;by&nbsp;fundus&nbsp;examination&nbsp;after&nbsp;a&nbsp;4-week&nbsp;waiting&nbsp;period&nbsp;accompanied&nbsp;by&nbsp;hyperglycaemia,&nbsp;and&nbsp;four&nbsp;different&nbsp;experimental&nbsp;groups&nbsp;were&nbsp;formed&nbsp;(<strong>Group&nbsp;1:</strong>&nbsp;Control,&nbsp;<strong>Group&nbsp;2:</strong>&nbsp;DR+PBS,&nbsp;<strong>Group&nbsp;3:</strong>&nbsp;DR+MKH&nbsp;-Exo&nbsp;intravitreal&nbsp;injection,&nbsp;<strong>Group&nbsp;4:</strong>&nbsp;DR+MKH-Exo&nbsp;subtenon&nbsp;injection).&nbsp;Subsequently,&nbsp;characterised&nbsp;exosomes&nbsp;isolated&nbsp;from&nbsp;adipose-derived&nbsp;MSCs&nbsp;were&nbsp;administered&nbsp;to&nbsp;the&nbsp;experimental&nbsp;groups&nbsp;at&nbsp;the&nbsp;specified&nbsp;dose&nbsp;and&nbsp;via&nbsp;two&nbsp;different&nbsp;injection&nbsp;types.&nbsp;For&nbsp;the&nbsp;molecular-level&nbsp;analysis&nbsp;of&nbsp;treatment&nbsp;efficacy,&nbsp;pro-inflammatory&nbsp;cytokines&nbsp;(VEGF,&nbsp;TNF-α,&nbsp;and&nbsp;IL1-β)&nbsp;were&nbsp;analysed&nbsp;using&nbsp;the&nbsp;ELISA&nbsp;method,&nbsp;and&nbsp;retina-related&nbsp;genes&nbsp;were&nbsp;analysed&nbsp;using&nbsp;qRT-PCR.&nbsp;Retinal&nbsp;tissue&nbsp;integrity&nbsp;and&nbsp;morphological&nbsp;changes&nbsp;were&nbsp;examined&nbsp;using&nbsp;Haematoxylin-Eosin&nbsp;(H&amp;E)&nbsp;staining,&nbsp;while&nbsp;the&nbsp;level&nbsp;of&nbsp;cellular&nbsp;apoptosis&nbsp;was&nbsp;examined&nbsp;using&nbsp;the&nbsp;TUNEL&nbsp;and&nbsp;Western&nbsp;Blot&nbsp;methods.</p><p>Our&nbsp;results&nbsp;demonstrate&nbsp;that&nbsp;subtenon&nbsp;administration&nbsp;of&nbsp;MKH-Exo&nbsp;provides&nbsp;superior&nbsp;therapeutic&nbsp;efficacy&nbsp;in&nbsp;alleviating&nbsp;retinal&nbsp;damage&nbsp;and&nbsp;inflammation&nbsp;in&nbsp;diabetic&nbsp;retinopathy.&nbsp;Subtenon&nbsp;administration&nbsp;has&nbsp;been&nbsp;assessed&nbsp;as&nbsp;a&nbsp;potentially&nbsp;clinically&nbsp;effective&nbsp;strategy&nbsp;for&nbsp;exosome-based&nbsp;therapies,&nbsp;reducing&nbsp;the&nbsp;risk&nbsp;of&nbsp;complications&nbsp;compared&nbsp;to&nbsp;intravitreal&nbsp;injection.</p><p><strong>Keywords:</strong>&nbsp;Diabetes,&nbsp;Diabetic&nbsp;retinopathy,&nbsp;Mesenchymal&nbsp;stem&nbsp;cell-derived&nbsp;exosome,&nbsp;Intravitreal&nbsp;injection,&nbsp;Subtenon&nbsp;injection</p>

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