Population differences in elastin maturation in optic nerve head tissue and astrocytes.

Area of Science:

• Ophthalmology
• Genetics
• Biochemistry

Background:

• Glaucomatous optic neuropathy involves extracellular matrix remodeling and elastic fiber disorganization in the optic nerve head (ONH).
• Significant disparities exist in the prevalence of glaucomatous optic neuropathy between African Americans (AAs) and Caucasian Americans (CAs).

Purpose of the Study:

• To investigate racial differences in elastin synthesis and maturation in the ONH of healthy African American and Caucasian American donors.
• To establish a foundation for understanding racial variations in susceptibility to elevated intraocular pressure.

Main Methods:

• Desmosine radioimmunoassay to quantify mature elastin in ONHs.
• Immunofluorescent staining to analyze elastic fiber distribution.
• Quantitative PCR and immunoblot analysis to assess elastin and lysyl oxidase mRNA and protein expression in ONH astrocytes.

Main Results:

• ONHs from AA donors exhibited significantly lower levels of mature elastin (desmosine) compared to CA donors.
• Astrocytes from AA individuals showed elevated elastin mRNA and tropoelastin synthesis but reduced inclusion of exon 23 in elastin mRNA.
• Lysyl oxidase-like 2 (LOXL2) mRNA levels were significantly lower in astrocytes from AA donors compared to CA donors.

Conclusions:

• Reduced elastin cross-linking and decreased LOXL2 expression contribute to lower mature elastin levels in the ONHs of healthy AAs.
• ELN and LOXL2 are proposed as candidate genes for population-specific genetic risk of primary open-angle glaucoma (POAG).