Parity Attenuates Intraepithelial Corneal Sensory Nerve Loss in Female Mice

Abstract

Aging impacts the ocular surface and reduces intraepithelial corneal nerve (ICN) density in male and female mice. Many researchers use retired breeders to study naturally aged female mice. Yet, the impact of parity and the length of time since breeders were retired on age-related changes in the intraepithelial corneal nerves is not known. Here we study 2 month (M) nulliparous (NP) females as well as 9M, 10M, and 11M NP and multiparous (MP) female mice to determine whether parity impacts the age-related decline seen in corneal axon density; 9M male mice are also included in these assessments. After showing that parity attenuates age-related loss in axon density, we also assess the impact of parity on corneal epithelial cell proliferation and find that it impacts cell proliferation and axon density normalized by cell proliferation. Stromal nerve arborization is also impacted by aging with parity enhancing stromal nerves in older mice. qPCR was performed on 20 genes implicated in ICN density using corneal epithelial RNA isolated from 10M NP and MP mice and showed that NGF expression was significantly elevated in MP corneal epithelium. Corneal sensitivity was significantly higher in 9M MP mice compared to NP mice and increased sensitivity in MP mice was accompanied by increased nerve terminals in the apical and middle cell layers. Together, these data show that parity in mice attenuates several aspects of the age-related decline seen on the ocular surface by retaining sensory axons and corneal sensitivity as mice age.

Modulation of Oxidative Stress and Inflammation in the Aged Lacrimal Gland

“…56e58 VEGF is secreted in tears of normal subjects, 59 and increased levels are found in tears of diabetic patients who progressed to diabetic retinopathy. 60 The sharp decrease in VEGF in tears of aged mice corresponded to the same time points when decreased corneal innervation and corneal sensitivity are observed, 61,62 suggesting loss of VEGF in tears might facilitate corneal neuron loss, although the precise mechanisms need further investigation.…”