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Updated: Feb 2, 2026

Induction of Retinal Ischemia-Reperfusion Injury in a Mouse Eye Model
Published on: December 20, 2024
Involvement of HDAC6 in ischaemia and reperfusion-induced rat retinal injury
Haihong Yuan1, Hui Li2,3, Ping Yu2
1Department of Pharmacy, Shanghai University of Medicine & Health Science, Shanghai, China.
Insights
Histone deacetylase 6 (HDAC6) inhibition protects retinal cells from injury. Tubacin, an HDAC6 inhibitor, reduced cell death and promoted survival in a retinal ischemia-reperfusion injury model, suggesting a therapeutic target for glaucoma.
Area of Science:
- Neuroscience
- Ophthalmology
- Molecular Biology
Background:
- Histone deacetylases 6 (HDAC6) are implicated in neurodegeneration.
- The role of HDAC6 in retinal degenerative conditions is largely unknown.
- Retinal ischemia-reperfusion (I/R) injury models provide insights into neurodegenerative processes.
Purpose of the Study:
- To investigate the role of HDAC6 in retinal I/R injury.
- To evaluate the therapeutic potential of HDAC6 inhibition in retinal neurodegeneration.
Main Methods:
- Retinal pathology assessed using H&E staining.
- HDAC6 expression and activity measured via Western blotting and colorimetric assays.
- Apoptosis and autophagy markers quantified using Western blotting and RT-PCR.
Main Results:
- HDAC6 inhibition with tubacin ameliorated I/R-induced retinal thinning and increased retinal ganglion cell (RGC) survival.
- Tubacin attenuated I/R-mediated apoptosis and enhanced autophagy-related protein expression.
- The protective effects of tubacin were linked to acetylated α-tubulin.
Conclusions:
- Tubacin demonstrates neuroprotective effects in a model of retinal I/R injury.
- HDAC6 inhibition represents a promising therapeutic strategy for glaucoma and other retinal neurodegenerative diseases.
Background:
The role of histone deacetylases 6 (HDAC6) has been elucidated in various neurodegenerative diseases. However, the effect of HDAC6 on retinal degenerative processes remains unknown. The aim of this study was to elucidate the potential role of HDAC6 in the retinal ischaemia and reperfusion (I/R) injury model.
Methods:
The retinal pathological lesion was evaluated by haematoxylin and eosin (H&E) staining. HDAC expression or activity was detected by immunohistochemistry, Western blotting assays or colorimetric assays. The expression of apoptotic- and autophagic- related proteins were quantified by Western blotting and RT-PCR. The expression of peroxiredoxin 2 (Prx2) was determined by RT-PCR and ELISA. The levels of acetylated α-tubulin and acetylated histone 3 in the retina were assayed by Western blotting.
Results:
We found that I/R-induced reduction of the retinal thickness was ameliorated, and the survival of RGCs was increased by the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) as well as by tubacin (an HDAC6 selective inhibitor). The decreased expression of THY (thymus cell antigen) in the I/R-induced retinas was also reversed by TSA and tubacin. Elevated HDAC6 expression and activity in the retina from I/R injury were significantly inhibited by tubacin, which also attenuated I/R-mediated apoptosis by decreasing TUNEL-positive RGCs and Bax expression and increasing Bcl-2 expression. Additionally, tubacin increased the expression of autophagy-related gene Beclin 1 and microtubule-associated protein 1 light chain 3B (LC3B) and the levels of Prx2. Furthermore, the protective effect of tubacin was associated with acetylated α-tubulin and was independent of acetylated histone 3.
Conclusions:
Our findings suggest that tubacin exhibits neuroprotective effects after I/R retinal injury, and HDAC6 may be a potential therapeutic target for the retinal neurodegenerative disease of glaucoma.
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