β -actin is essential for structural integrity and physiological function of the retina

Area of Science:

• Cell Biology
• Ophthalmology
• Genetics

Background:

• The non-muscle beta-actin gene (Actb) is essential for embryonic development, leading to lethality when absent.
• Mice with a beta-actin to gamma-actin gene replacement are viable and phenotypically normal in youth.
• The long-term effects of this actin gene replacement on specific tissues, like the retina, remain largely unexplored.

Approach:

• Investigated the impact of beta-actin to gamma-actin gene replacement on retinal structure and function during aging.
• Examined age-related changes in retinal pigment epithelium (RPE), photoreceptor outer segments (OS), and associated cellular components.
• Analyzed alterations in F-actin binding partners critical for cytoskeletal integrity and cellular processes.

Key Points:

• Aging mice with beta-actin replaced by gamma-actin exhibit accelerated retinal degeneration.
• Specific defects include RPE microvilli elongation, mitochondrial dysfunction, and bulging photoreceptor outer segments.
• Reduced transducin concentration, decreased light sensitivity, and subretinal accumulation of autofluorescent microglia were observed.
• Changes in F-actin binding with key proteins like ezrin, myosin, talin, and vinculin were noted, impacting cell adhesion and OS phagocytosis.

Conclusions:

• Beta-actin protein plays an indispensable role in preserving normal retinal structure and function throughout the aging process.
• Gamma-actin cannot fully compensate for beta-actin's functions in the retina, particularly concerning age-related maintenance.
• The study highlights the critical necessity of beta-actin for long-term ocular health and function.