Scleral structural alterations associated with chronic experimental intraocular pressure elevation in mice

Area of Science:

• Ophthalmology
• Biomaterials Science
• Connective Tissue Biology

Background:

• The sclera, the eye's protective outer layer, provides structural integrity.
• Understanding scleral changes in glaucoma is crucial for developing effective treatments.
• Previous studies have not fully elucidated the dynamic structural alterations in the sclera during experimental glaucoma.

Purpose of the Study:

• To investigate the structural modifications of the sclera in response to chronic elevated intraocular pressure in a mouse model of glaucoma.
• To compare scleral changes across different mouse strains with varying genetic backgrounds.

Main Methods:

• Bead-induced glaucoma was established in C57BL/6 (B6), CD1, and collagen 8α2 mutant (Aca23) mice.
• Scleral thickness, collagen lamellar structure, and collagen fibril diameter were analyzed using electron and confocal microscopy.
• Second harmonic generation imaging was employed to assess collagen fibril organization.

Main Results:

• Glaucoma induction led to a significant thinning of the sclera in both CD1 and B6 mice.
• Electron microscopy revealed increased scleral thickness in fixed specimens after glaucoma, with alterations in lamellar orientation and an increase in cellular and cross-section lamellae.
• Collagen fibril analysis showed a shift towards smaller fibrils and a decrease in larger ones, alongside altered collagen patterns in glaucomatous eyes.

Conclusions:

• The sclera exhibits dynamic structural responses to experimental glaucoma, including changes in nonfibrillar components, lamellar arrangement, and collagen fibril size distribution.
• These dynamic scleral alterations, rather than baseline anatomy, appear more critical in determining susceptibility to glaucomatous damage.
• The findings suggest that targeting these dynamic scleral changes could be a therapeutic strategy for glaucoma.