Loss of RhoB Alters Retinal Function and Intraocular Pressure Regulation

Document Type

Article

Publication Date

6-2025

Abstract

Purpose : RhoB, a small GTPase, is involved in apoptosis, intracellular transport, and angiogenesis, with implications in cancer, diabetes, and retinopathy of prematurity. RhoA, part of the same Rho GTPase family as RhoB has been previously studied in its role of intraocular pressure. Previous studies have shown RhoA’s role in the Rho/ROCK pathway regulating intraocular pressure. However, RhoB’s role in the retina, especially during stress or aging, remains underexplored. Previous studies have shown using supplemental oxygen during the critical period reduces photoreceptor death, while hypoxia increases it. This study investigates how the absence of RhoB (RhoB-/-) affects retinal neurons in response to oxygen fluctuations during retinal development and aging.

Methods : C57Bl/6JRhoB -/- (RhoB -/-) and control wild type (C57Bl/6J) mice were exposed to varying oxygen conditions (12% oxygen, 21% oxygen, and 75% oxygen) from postnatal day 7 (P7) to P20. Immunofluorescence was performed at P12, P16, P28, and 1 year to quantify apoptotic cell death. Scotopic electroretinography (ERG) was conducted at P27 and 1 year. Intraocular pressure (IOP) was measured in mice at 4 weeks and aging mice (9-12months) using a tonometer.

Results : At P12, RhoB-/- mice exhibited significantly increased apoptotic cell death in the ONL, INL, and GCL compared to controls at 21% oxygen. By P28, RhoB-/- mice showed more extensive GCL cell death across all oxygen conditions (p< 0.05). Although visual function was impaired in RhoB-/- mice at 21% oxygen and 12% oxygen. 75% oxygen partially restored function. In 1 year old mice, RhoB-/- had 4 times more photoreceptor death and significantly elevated IOP (18.3 mmHg in RhoB-/- vs. 11.9 mmHg in controls). Electroretinography revealed poorer retinal function in RhoB-/- mice at P27 and 1 year, as indicated by reduced A- and B-wave amplitudes.

Conclusions : RhoB-/- mice display significant retinal degeneration, including increased cell death and impaired visual function. Being in 75% oxygen during the critical period partially alleviates these effects. Additionally, RhoB-/- mice experience elevated intraocular pressure and progressive visual dysfunction with aging. Further histological analysis is needed to determine the underlying retinal changes and the mechanisms leading to ocular hypertension in these mice.

Purpose : RhoB, a small GTPase, is involved in apoptosis, intracellular transport, and angiogenesis, with implications in cancer, diabetes, and retinopathy of prematurity. RhoA, part of the same Rho GTPase family as RhoB has been previously studied in its role of intraocular pressure. Previous studies have shown RhoA’s role in the Rho/ROCK pathway regulating intraocular pressure. However, RhoB’s role in the retina, especially during stress or aging, remains underexplored. Previous studies have shown using supplemental oxygen during the critical period reduces photoreceptor death, while hypoxia increases it. This study investigates how the absence of RhoB (RhoB-/-) affects retinal neurons in response to oxygen fluctuations during retinal development and aging.

Methods : C57Bl/6JRhoB -/- (RhoB -/-) and control wild type (C57Bl/6J) mice were exposed to varying oxygen conditions (12% oxygen, 21% oxygen, and 75% oxygen) from postnatal day 7 (P7) to P20. Immunofluorescence was performed at P12, P16, P28, and 1 year to quantify apoptotic cell death. Scotopic electroretinography (ERG) was conducted at P27 and 1 year. Intraocular pressure (IOP) was measured in mice at 4 weeks and aging mice (9-12months) using a tonometer.

Results : At P12, RhoB-/- mice exhibited significantly increased apoptotic cell death in the ONL, INL, and GCL compared to controls at 21% oxygen. By P28, RhoB-/- mice showed more extensive GCL cell death across all oxygen conditions (p< 0.05). Although visual function was impaired in RhoB-/- mice at 21% oxygen and 12% oxygen. 75% oxygen partially restored function. In 1 year old mice, RhoB-/- had 4 times more photoreceptor death and significantly elevated IOP (18.3 mmHg in RhoB-/- vs. 11.9 mmHg in controls). Electroretinography revealed poorer retinal function in RhoB-/- mice at P27 and 1 year, as indicated by reduced A- and B-wave amplitudes.

Conclusions : RhoB-/- mice display significant retinal degeneration, including increased cell death and impaired visual function. Being in 75% oxygen during the critical period partially alleviates these effects. Additionally, RhoB-/- mice experience elevated intraocular pressure and progressive visual dysfunction with aging. Further histological analysis is needed to determine the underlying retinal changes and the mechanisms leading to ocular hypertension in these mice.

Comments

This abstract was published in Investigative Ophthalmology & Visual Science, Volume 66, Issue 8.

The published version is available at https://iovs.arvojournals.org/article.aspx?articleid=2807673.

Copyright © 2025. CC BY-NC-ND 4.0.

Publication Title

Investigative Ophthalmology and Visual Science

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