{
  "abstract": "Fuchs Endothelial Corneal Dystrophy (FECD) is characterized by progressive corneal endothelial cell loss and the formation of corneal guttae. Currently, there is a global shortage of donor corneas and new strategies are needed to reduce the need for corneal transplantation. While adeno-associated viruses (AAVs) have the capacity to deliver anti-apoptotic genes to human corneal endothelial cells (CECs), this has not been fully explored as a therapeutic strategy for FECD. In this study, we evaluated the transduction efficiency of self-complementary (sc-) and single-stranded (ss-) AAV2 serotypes in human CECs and ex vivo tissues and assessed whether AAV-mediated expression of Bcl-xL could attenuate apoptosis in FECD. Seventeen scAAV2 serotypes were screened for transduction efficiency in normal human CECs via green fluorescent protein (GFP) expression. The top 4 AAV2 serotypes were further evaluated in FECD cell lines, healthy cadaveric donor specimens, and FECD patient specimens. FECD cell lines were transduced with anti-apoptotic ssAAV2/5-Bcl-xL (AAV2/5-CAG-eGFP-P2A-BCLXL) and treated with etoposide to induce apoptosis. We found that scAAV2/5 demonstrated high transduction efficiency across all normal and FECD cell lines and tissues. We observed that ssAAV2/5-mediated expression of Bcl-xL provided significant protection against etoposide-induced apoptosis in FECD CECs (71.68%{+/-}0.69 vs 23.96%{+/-}8.88%, p=0.018). Our findings show that AAVs have the potential for therapeutic gene delivery to the human corneal endothelium, and that targeting the Bcl-xL mediated apoptotic pathway can be further explored as a therapeutic for FECD.",
  "abstract_shown": true,
  "affiliations": [
    "Sunnybrook Research Institute"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "N. Little"
    },
    {
      "name": "J. Yan"
    },
    {
      "name": "N. Dhupar"
    },
    {
      "affs": [
        0
      ],
      "name": "S. Ong Tone"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/47zxrm111td69.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.01.748650",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748650v1.full",
  "id": "47zxrm111td69",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748650v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cell biology"
    ],
    [
      "openalex",
      "1311|Virus-based gene therapy research"
    ]
  ],
  "openalex": "W7207727456",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748650v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/47zxrm111td69.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:52Z",
      "native_id": "10.64898/2026.09.01.748650",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748650v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "Adeno-Associated Virus Mediated Expression of Bcl-xL Attenuates Apoptosis in Fuchs Endothelial Corneal Dystrophy",
  "title_text": "Adeno-Associated Virus Mediated Expression of Bcl-xL Attenuates Apoptosis in Fuchs Endothelial Corneal Dystrophy",
  "type": "preprint",
  "updated_at": "2026-10-30T12:18:52Z",
  "url": "https://research.draconitic.com/paper/47zxrm111td69",
  "venue": "bioRxiv",
  "versions": []
}