bims-mideyd Biomed News
on Mitochondrial dysfunction in eye diseases
Issue of 2025–05–04
three papers selected by
Rajalekshmy “Raji” Shyam, Indiana University Bloomington



  1. Aging Cell. 2025 Apr 28. e70081
      Age is a primary risk factor for chronic conditions, including age-related macular degeneration (AMD). Impairments in autophagy processes are implicated in AMD progression, but the extent of autophagy's contribution and its therapeutic potential remain ambiguous. This study investigated age-associated transcriptomic changes in autophagy pathways in the retinal pigment epithelium (RPE) and evaluated the protective effects of topical trehalose, an autophagy-enhancing small molecule, against light-induced outer retinal degeneration in mice. Transcriptomic analysis of human RPE/choroid and mouse RPE revealed consistent downregulation of autophagy pathways with age, alongside variable changes as AMD severity progressed. Given the age- and AMD-associated perturbation of autophagy pathways, we examined trehalose treatment in vitro, which enhanced autophagic flux and restored mitochondrial respiratory function in primary murine RPE cells exposed to oxidative stress. In vivo, topical trehalose improved autophagy-lysosome activity in mouse RPE, as demonstrated by elevated LC3B turnover and SQSTM1/p62 degradation. Furthermore, trehalose eyedrops protected mice from light-induced damage to the RPE and photoreceptors, preserving outer nuclear layer thickness, RPE morphology, and junctional F-actin organization. Taken together, the data support that age-related decline and severe dysregulation in autophagy contributed to AMD progression. By restoring autophagic flux, topical trehalose demonstrates therapeutic potential to address early autophagy-related pathological changes in AMD.
    Keywords:  aging; autophagy; oxidative stress; retinal degeneration; retinal pigment epithelium; topical administration; trehalose
    DOI:  https://doi.org/10.1111/acel.70081
  2. Methods Mol Biol. 2025 ;2924 235-248
      We have developed an image J macro to analyze pigmentation level in iPSC-derived retinal pigment epithelial cells from bright-field images. Human iPSC-derived retinal pigment epithelial cells were treated with hydroquinone to induce hyperpigmentation, and untreated cells were used as controls for the study. The Image analysis results were validated by estimating melanin spectrophotometrically, after lysing the cells. The developed image analysis method will be useful for screening drugs/compounds that induce hyper/hypo pigmentation in cultured iPSC-derived RPE cells.
    Keywords:  Human iPSC; Hyperpigmentation; Image analysis; RPE differentiation
    DOI:  https://doi.org/10.1007/978-1-0716-4530-7_17
  3. Methods Mol Biol. 2025 ;2924 101-112
      We have developed a method to reliably generate retinal pigment epithelium (RPE) in bulk from human induced pluripotent stem cells (iPSCs). These iPSC-RPE showed a typical RPE-like morphology with pigmentation and expressed typical RPE markers. The iPSC-RPE also show a transepithelial electrical resistance and can phagocytose photoreceptor outer segments, indicating that they are also functional. Large quantities of iPSC-RPE can be generated with this method through serial expansion for disease modeling and high-throughput screenings.
    Keywords:  Human-induced pluripotent stem (hiPS) cells; Retinal differentiation; Retinal pigment epithelium (RPE)
    DOI:  https://doi.org/10.1007/978-1-0716-4530-7_8