{
  "abstract": "Photoreceptor degeneration arises from diverse genetic and acquired insults, yet oxidative stress, mitochondrial dysfunction, and sterile inflammation repeatedly converge on membrane injury and irreversible cell loss. Inflammasome activation is frequently described as retinal pyroptosis, although upstream markers alone neither establish gasdermin-dependent lysis nor identify the executing cell. Rather than treating retinal pyroptosis as a single cell-autonomous pathway, we distinguish a myeloid gasdermin D (GSDMD) inflammatory relay from a photoreceptor-intrinsic gasdermin E (GSDME) lytic amplification program and evaluate potential interventions according to direct retinal evidence, cellular specificity, and translational readiness. GSDMD is best supported in microglia and subretinal macrophages, where inflammasome-caspase-1 signaling promotes cytokine and extracellular-vesicle release and can worsen secondary photoreceptor injury. Recent evidence in TREM2-deficient rd10 retina further supports GSDMD as a functional disease modifier, while remaining context specific. By contrast, GSDME has direct loss-of-function support in all-trans-retinal overload, in which caspase-3-dependent cleavage increases membrane rupture and is associated with mitochondrial oxidative burden and ferroptotic susceptibility. We compare NLRP3/caspase-1, interleukin-1, GSDMD pore, GSDME, and redox-directed strategies against five translational gates: target engagement, ocular exposure, cell specificity, delivery feasibility, and safety. This evidence-graded framework identifies promising pharmacological entry points while preserving the distinction between mechanistic plausibility and retinal target readiness.",
  "abstract_shown": true,
  "affiliations": [
    "Hunan University of Chinese Medicine",
    "Institute of Ophthalmology and Otolaryngology of Chinese Medicine",
    "Changsha Centre for Innovation in Traditional Chinese Medicine Techniques for the Prevention and Treatment of Retinal Diseases and Visual Function Protection"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Ying Deng"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Yasha Zhou"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Pai Zhou"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Li Xiao"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Jing Lu"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Qinghua Peng"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Yijing Yang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/erj1khq5xc0fz.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1981060",
  "fulltext_url": null,
  "id": "erj1khq5xc0fz",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1981060/full",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-29",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/erj1khq5xc0fz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:08Z",
      "native_id": "10.3389/fphar.2026.1981060",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1981060/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:1663-9812",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Compartment-specific roles of gasdermin D and E in photoreceptor degeneration: evidence and pharmacological implications",
  "title_text": "Compartment-specific roles of gasdermin D and E in photoreceptor degeneration: evidence and pharmacological implications",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T00:21:07Z",
  "url": "https://research.draconitic.com/paper/erj1khq5xc0fz",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}