Effect of TRPV1 activation on the accommodative changes in monkey crystalline lens shape, power, and stiffness

Abstract

Purpose : In non-accommodating lenses, reducing zonular tension alters lens water transport via the activation of the mechanosensitive channel TRPV1. (Chen et al., IOVS, 2019; Petrova et al., Mol Sci, 2023) This study tested the effect of TRPV1 activator, capsaicin, on lens shape, power, and stiffness in the monkey lens that can accommodate.

Methods : Four lenses from two cynomolgus monkeys (Macaca fascicularis, ages 5.25, 5.67 years; post-mortem time 24±18 hours) were mounted in a motorized lens stretcher. (Nankivil et al,. IOVS, 2015) Stretching experiments were performed on each lens submerged in Dulbecco's Modified Eagle's Medium (DMEM) where the outer scleral shell was displaced 2.5 mm radially in 0.25 mm steps. Lens diameter, thickness, power, and stretching force were measured at each stretch position for each experiment run. The media was then swapped for DMEM+10μM capsaicin and stretching experiments were repeated every 30 minutes for 2 hours. The axial shift of the tissue chamber wall from the OCT images was used to calculate the average refractive index of the lens. (Uhlhorn et al., Vis Res, 2008) The changes in each parameter with stretching in DMEM (control) and capsaicin over time were compared.

Results : The unstretched lens diameter decreased and thickness slightly increased with the submersion in capsaicin while the fully stretched lens shape remained unchanged. The unstretched lens power decreased by 1.7 D, on average, with capsaicin and did not return to baseline, while the fully stretched power remained unchanged. The maximum force required to stretch the tissue decreased by 18%, on average, after 2 hours in capsaicin. The lens average refractive index was 1.418±0.002 and did not change with capsaicin.

Conclusions : Capsaicin produced a consistent change in the accommodated lens shape. The decrease in force required to stretch the tissue with the capsaicin treatment suggests that the transient increase in lens surface pressure induced by capsaicin causes the lens to become less stiff. These results provide insight into how activation of the mechanosensitive channels of the lens contribute to optical and mechanical changes.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.