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The mechanisms leading to neuro-retinal cell loss before vascular complications manifest in diabetes remain poorly understood. In this study, we investigated the neuronal RNA-binding protein HuD as a novel regulator of neuro-retinal degeneration in the early stage of diabetes. We determined the expression of HuD and alpha-crystallin A (CRYAA) in the retinal ganglion cell layer. HuD and CRYAA were down-regulated in the retinas of streptozotocin-induced diabetic rats and in neuro-retinal cells (R-28) treated with high glucose.\n                    <jats:italic>Cryaa<\/jats:italic>\n                    mRNA was identified as a novel target transcript of HuD, and we demonstrated that HuD post-transcriptionally regulates the expression of\n                    <jats:italic>Cryaa<\/jats:italic>\n                    mRNA by binding to its 3\u2032-untranslated region. Silencing and overexpression of HuD positively regulated the expressions of\n                    <jats:italic>Cryaa<\/jats:italic>\n                    mRNA and protein. We demonstrated that the increase in inflammatory cytokines such as TNF\u03b1, IL-1\u03b2, and IL-6 in R-28 cells under hyperglycemic conditions was a result of both CRYAA and HuD levels. Silencing HuD and CRYAA enhanced high glucose-induced R-28 cell death, whereas their overexpression alleviated this effect. HuD post-transcriptionally regulates CRYAA expression, influencing the function and viability of neuro-retinal cells under diabetic conditions. Our results suggest that the HuD\/CRYAA axis plays a crucial role in neuro-retinal cells and has the potential to serve as a prognostic factor and therapeutic target for diabetic neuro-retinal degeneration.\n                  <\/jats:p>","DOI":"10.1007\/s11010-025-05364-2","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T05:59:44Z","timestamp":1754978384000},"page":"6157-6170","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HuD and alpha-crystallin A axis protects neuro-retinal cells in early diabetes"],"prefix":"10.1007","volume":"480","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2483-806X","authenticated-orcid":false,"given":"Chongtae","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5150-5039","authenticated-orcid":false,"given":"Subeen","family":"Oh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2774-9997","authenticated-orcid":false,"given":"Young-Hoon","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"5364_CR1","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1111\/nyas.12412","volume":"1311","author":"SF Abcouwer","year":"2014","unstructured":"Abcouwer SF, Gardner TW (2014) Diabetic retinopathy: loss of neuroretinal adaptation to the diabetic metabolic environment. 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