Significant upregulation of small heat shock protein αA-crystallin in retinal detachment

Hamadmad, Sumaya; Shah, Manisha; Kusibati, Rania; Kim, Bongsu; Erickson, Brandon J.; Heisler-Taylor, Tyler; Bhattacharya, Sanjoy K.; Abdel‐Rahman, Mohamed H.; Cebulla, Colleen M.

doi:10.1016/j.exer.2019.107811

Cited by 3 publications

(3 citation statements)

References 29 publications

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“…Following experimental retinal detachment, α-crystallins were induced and accumulated in photoreceptor inner and outer segments. This localization is consistent with another study at later stages of retinal detachment that reported that αΑ-crystallin expression is highly increased compared to control and that its immunoreactivity is found primarily in the inner and outer segments of the photoreceptors, with slightly more diffuse staining in other retinal layers 15 . This is also consistent with another disease mostly impacting the outer retina, experimentally-induced uveitis, in which αA-Crystallin is also highly upregulated in the retina and is primarily localized in the photoreceptor inner segments 12 .…”

Section: Discussionsupporting

confidence: 92%

“…Consistent with the key role of αA-crystallin in the retina, a recent study by Hamadmad et al has reported that post retinal detachment αA-crystallin displayed the highest level of increase among all the other crystallins in the mouse. They also reported a signi cant increase in protein levels of αΑcrystallin in the vitreous of retinal detachment patients compared to their control counterparts 15 .…”

Section: Discussionmentioning

confidence: 95%

“…Crystallins have been shown to be highly upregulated in a rodent model of retinal tear, consistent with a potential protective response in the context of retinal injury 14 . Additionally, a study by Hamadmad et al, 2019 reported that αΑ-crystallin is signi cantly upregulated following RD in mouse and humans 15 .…”

Section: Introductionmentioning

confidence: 99%

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Alpha-crystallins protect photoreceptors during retinal detachment through FAIM2 regulation

Besirli

Nath

Yao

et al. 2022

Preprint

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We evaluated the role of α-crystallin in photoreceptor survival in an experimental model of retinal detachment, and its association with Fas apoptosis inhibitory molecule 2 (FAIM2). Retina/RPE separation was induced in rat and mouse eyes by the subretinal injection of hyaluronic acid, 1%. Retinal tissues were analyzed for the presence αA-crystallin and αB-crystallin proteins using immunohistochemistry and immunoblot. Indices of photoreceptor death were analyzed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining and cell counts. The 661W cells subjected to FasL were used as a cell model of photoreceptor degeneration to assess the mechanisms of the protective effect of αA-crystallin and its phosphorylation on T148. In addition to the associated cell-death, FAIM2 and αA-crystallin interaction were evaluated using co-immunoprecipitation assay. α-Crystallin protein levels were rapidly induced in response to retinal detachment, with αA-crystallin playing a particularly important role in protecting photoreceptors during retinal detachment. Our data also shows that FAIM2, an intrinsic neuroprotective protein in photoreceptors, interacts with α-crystallins following retinal detachment. Mechanistically, our work also demonstrated that the phosphorylation of αA-crystallin is essential for the interaction of αA-crystallin with FAIM2 and their neuroprotective effect. Thus, αA-crystallin is involved in the regulation of photoreceptor survival during retinal detachment, playing a key role in the stabilization of FAIM2, an important modulator of photoreceptor cell survival under chronic stress condition.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 95%

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Alpha-crystallins protect photoreceptors during retinal detachment through FAIM2 regulation

Besirli

Nath

Yao

et al. 2022

Preprint

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Vitreous Humor Proteome: Targeting Oxidative Stress, Inflammation, and Neurodegeneration in Vitreoretinal Diseases

et al. 2022

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Oxidative stress is defined as an unbalance between pro-oxidants and antioxidants, as evidenced by an increase in reactive oxygen and reactive nitrogen species production over time. It is important in the pathophysiology of retinal disorders such as diabetic retinopathy, age-related macular degeneration, retinal detachment, and proliferative vitreoretinopathy, which are the focus of this article. Although the human organism’s defense mechanisms correct autoxidation caused by endogenous or exogenous factors, this may be insufficient, causing an imbalance in favor of excessive ROS production or a weakening of the endogenous antioxidant system, resulting in molecular and cellular damage. Furthermore, modern lifestyles and environmental factors contribute to increased chemical exposure and stress induction, resulting in oxidative stress. In this review, we discuss the current information about oxidative stress and the vitreous proteome with a special focus on vitreoretinal diseases. Additionally, we explore therapies using antioxidants in an attempt to rescue the body from oxidation, restore balance, and maximize healthy body function, as well as new investigational therapies that have shown significant therapeutic potential in preclinical studies and clinical trial outcomes, along with their goals and strategic approaches to combat oxidative stress.

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HSPB4/CRYAA Protect Photoreceptors during Retinal Detachment in Part through FAIM2 Regulation

Besirli,

Nath,

Yao

et al. 2024

Neurology International

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Our previous study discussed crystallin family induction in an experimental rat model of retinal detachment. Therefore, we attempted to evaluate the role of α-crystallin in photoreceptor survival in an experimental model of retinal detachment, as well as its association with the intrinsically neuroprotective protein Fas-apoptotic inhibitory molecule 2 (FAIM2). Separation of retina and RPE was induced in rat and mouse eyes by subretinal injection of hyaluronic acid. Retinas were subsequently analyzed for the presence αA-crystallin (HSPB4) and αB-crystallin (HSPB5) proteins using immunohistochemistry and immunoblotting. Photoreceptor death was analyzed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining and cell counts. The 661W cells subjected to FasL were used as a cell model of photoreceptor degeneration to assess the mechanisms of the protective effect of αA-crystallin and its dependence on its phosphorylation on T148. We further evaluated the interaction between FAIM2 and αA-crystallin using a co-immunoprecipitation assay. Our results showed that α-crystallin protein levels were rapidly induced in response to retinal detachment, with αA-crystallin playing a particularly important role in protecting photoreceptors during retinal detachment. Our data also show that the photoreceptor intrinsically neuroprotective protein FAIM2 is induced and interacts with α-crystallins following retinal detachment. Mechanistically, our work also demonstrated that the phosphorylation of αA-crystallin is important for the interaction of αA-crystallin with FAIM2 and their neuroprotective effect. Thus, αA-crystallin is involved in the regulation of photoreceptor survival during retinal detachment, playing a key role in the stabilization of FAIM2, serving as an important modulator of photoreceptor cell survival under chronic stress conditions.

show abstract

Significant upregulation of small heat shock protein αA-crystallin in retinal detachment

Cited by 3 publications

References 29 publications

Alpha-crystallins protect photoreceptors during retinal detachment through FAIM2 regulation

Alpha-crystallins protect photoreceptors during retinal detachment through FAIM2 regulation

Vitreous Humor Proteome: Targeting Oxidative Stress, Inflammation, and Neurodegeneration in Vitreoretinal Diseases

HSPB4/CRYAA Protect Photoreceptors during Retinal Detachment in Part through FAIM2 Regulation

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