Evidence map›Paper›PMID 42143320›Full record

ArticleMolecular neurodegeneration2026

Pharmacological restoration of impaired autophagy in retinal ganglion cells prevents abnormal mitochondrial accumulation and glaucomatous neurodegeneration.

Prabhavathi Maddineni, Balasankara Reddy Kaipa, Bindu Kodati, Karthikeyan Kesavan, Linya Li, J Cameron Millar, Sam Yacoub, Ramesh B Kasetti, Abbot F Clark, Gulab S Zode

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Article in Molecular neurodegeneration, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Prabhavathi Maddineni *Department of Ophthalmology, School of Medicine, University of Missouri, 1 Hospital Dr, Columbia, MO, 65212, USA. pmbnv@health.missouri.edu.
Balasankara Reddy Kaipa *Gavin Herbert Eye Institute-Center for Translational Vision Research, Department of Ophthalmology, Department of Physiology and Biophysics, Irvine School of Medicine, University of California, 829 Health Sciences Rd, Irvine, CA, 92697, USA.
Bindu KodatiDepartment of Pharmacology and Neuroscience and North Texas Eye Research Institute, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, 76107, USA.
Karthikeyan KesavanDepartment of Ophthalmology, School of Medicine, University of Missouri, 1 Hospital Dr, Columbia, MO, 65212, USA.
Linya LiDepartment of Pharmacology and Neuroscience and North Texas Eye Research Institute, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, 76107, USA.
J Cameron MillarDepartment of Pharmacology and Neuroscience and North Texas Eye Research Institute, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, 76107, USA.
Sam YacoubDepartment of Pharmacology and Neuroscience and North Texas Eye Research Institute, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, 76107, USA.
Ramesh B KasettiDepartment of Pharmacology and Neuroscience and North Texas Eye Research Institute, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, 76107, USA.
Abbot F ClarkDepartment of Pharmacology and Neuroscience and North Texas Eye Research Institute, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, 76107, USA.
Gulab S ZodeGavin Herbert Eye Institute-Center for Translational Vision Research, Department of Ophthalmology, Department of Physiology and Biophysics, Irvine School of Medicine, University of California, 829 Health Sciences Rd, Irvine, CA, 92697, USA. gzode@hs.uci.edu.

Funding

Crosstalk Between Unfolded Protein Response and Autophagy for the Treatment of GlaucomaR01EY026177 · NEI · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI ZODE, GULAB · 2016 to 2025
$3.8M
Impaired TRVP4-eNOS signaling in TM contributes to glaucomaR01EY034238 · NEI · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI Swapnil K. Sonkusare, Gulab Zode · 2022 to 2026
$2.2M
Targeting ER Stress Pathway Using Sodium 4-Phenylbutyrate for the Treatment of POAGR01EY028616 · NEI · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI ZODE, GULAB · 2018 to 2021
$1.4M
The role of impaired mitophagy and mitochondrial dysfunction in glaucomatous neurodegenerationR00EY032982 · NEI · UNIVERSITY OF MISSOURI-COLUMBIA · PI Prabhavathi Maddineni · 2024 to 2026
$758k
The role of impaired mitophagy and mitochondrial dysfunction in glaucomatous neurodegenerationK99EY032982 · NEI · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI MADDINENI, PRABHAVATHI · 2021 to 2022
$199k
NEI NIH HHS K99 EY032982NEI NIH HHS R00 EY032982NEI NIH HHS R01 EY026177NEI NIH HHS R01 EY028616NEI NIH HHS R01 EY034238
6 · The paper itself

Abstract

backgroundProgressive loss of retinal ganglion cells (RGCs) and degeneration of optic nerve (ON) axons are the key pathological hallmarks of glaucoma, the leading cause of irreversible blindness. Elevated intraocular pressure (IOP), primarily due to dysfunction of the trabecular meshwork (TM), remains the most significant and only known modifiable risk factor. However, vision loss persists in some patients despite effective IOP control, highlighting the critical need to elucidate the mechanisms driving glaucomatous neurodegeneration. Emerging evidence links mitochondrial dysfunction to glaucomatous neurodegeneration, yet the precise mechanisms remain poorly defined. Here, we investigate whether defective autophagy/mitophagy, which removes damaged mitochondria, contributes to mitochondrial accumulation, oxidative stress, and neurodegeneration in glaucoma. We further explore the therapeutic potential of enhancing autophagy to improve mitochondrial turnover, mitigate RGC loss, and preserve visual function.

methodsGlucocorticoid (GC)-induced and myocilin (MYOC)-associated glaucoma mouse models were used to assess the expression of mitochondrial markers (TOM20/COX IV), oxidative DNA damage (8-OHdG), and mitophagy/autophagy-related proteins (p62, LC3, Phospho-ubiquitin (Ser65), and LAMP1) in retinal tissues. Transmission electron microscopy (TEM) was employed to analyze mitochondrial accumulation in glaucomatous ON. Mitophagy flux was assessed at early and late stages of neurodegeneration using mitophagy reporter Mt-Keima mice. The effect of RGC-specific autophagy deficiency on mitochondrial accumulation and neurodegeneration was further investigated using Atg5

resultsChronic IOP elevation led to increased mitochondrial accumulation, oxidative DNA damage, and impaired mitophagy/autophagy in glaucomatous retina. TEM analysis further confirmed the accumulation of structurally abnormal mitochondria in glaucomatous ON. In Mt-Keima mice, chronic IOP elevation significantly reduced mitophagy flux prior to RGC loss, indicating that mitophagy impairment precedes neurodegeneration. RGC-specific Atg5 deletion induced the accumulation of damaged mitochondria, leading to neurodegeneration in Atg5

conclusionOur study indicates impaired autophagy contributes to damaged mitochondrial accumulation and oxidative stress, leading to glaucomatous neurodegeneration. Enhancing autophagy in RGCs represents a promising therapeutic strategy to prevent glaucomatous neurodegeneration.

Indexed as

AutophagyGlaucomaMitochondriaRetinal Ganglion CellsAnimalsDisease Models, AnimalIntraocular PressureMiceMitophagyMyocilinOxidative StressMyocilinAutophagyGlaucomaIntraocular pressureMitochondrial dysfunctionMitophagyMouse models of glaucomaNeurodegenerationOptic neuropathyOxidative DNA damageTorin 2

Identifiers

PMID42143320
PMCPMC13242679

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.