Parity Attenuates Intraepithelial Corneal Sensory Nerve Loss in Female Mice

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 intr...

Full description

Bibliographic Details
Main Authors: Mary Ann Stepp, Sonali Pal-Ghosh, Gauri Tadvalkar, Cintia S. de Paiva
Format: Article
Language:English
Published: MDPI AG 2020-07-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/14/5172
_version_ 1797561760520077312
author Mary Ann Stepp
Sonali Pal-Ghosh
Gauri Tadvalkar
Cintia S. de Paiva
author_facet Mary Ann Stepp
Sonali Pal-Ghosh
Gauri Tadvalkar
Cintia S. de Paiva
author_sort Mary Ann Stepp
collection DOAJ
description 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.
first_indexed 2024-03-10T18:19:08Z
format Article
id doaj.art-ad5a054e8a5243ed8cfaa0951ec0ea41
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-10T18:19:08Z
publishDate 2020-07-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
spelling doaj.art-ad5a054e8a5243ed8cfaa0951ec0ea412023-11-20T07:29:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-012114517210.3390/ijms21145172Parity Attenuates Intraepithelial Corneal Sensory Nerve Loss in Female MiceMary Ann Stepp0Sonali Pal-Ghosh1Gauri Tadvalkar2Cintia S. de Paiva3Department of Anatomy and Regenerative Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USADepartment of Anatomy and Regenerative Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USADepartment of Anatomy and Regenerative Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USAOcular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX 77030, USAAging 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.https://www.mdpi.com/1422-0067/21/14/5172corneal sensory nervesagingpregnancymouseparitycorneal sensitivity
spellingShingle Mary Ann Stepp
Sonali Pal-Ghosh
Gauri Tadvalkar
Cintia S. de Paiva
Parity Attenuates Intraepithelial Corneal Sensory Nerve Loss in Female Mice
International Journal of Molecular Sciences
corneal sensory nerves
aging
pregnancy
mouse
parity
corneal sensitivity
title Parity Attenuates Intraepithelial Corneal Sensory Nerve Loss in Female Mice
title_full Parity Attenuates Intraepithelial Corneal Sensory Nerve Loss in Female Mice
title_fullStr Parity Attenuates Intraepithelial Corneal Sensory Nerve Loss in Female Mice
title_full_unstemmed Parity Attenuates Intraepithelial Corneal Sensory Nerve Loss in Female Mice
title_short Parity Attenuates Intraepithelial Corneal Sensory Nerve Loss in Female Mice
title_sort parity attenuates intraepithelial corneal sensory nerve loss in female mice
topic corneal sensory nerves
aging
pregnancy
mouse
parity
corneal sensitivity
url https://www.mdpi.com/1422-0067/21/14/5172
work_keys_str_mv AT maryannstepp parityattenuatesintraepithelialcornealsensorynervelossinfemalemice
AT sonalipalghosh parityattenuatesintraepithelialcornealsensorynervelossinfemalemice
AT gauritadvalkar parityattenuatesintraepithelialcornealsensorynervelossinfemalemice
AT cintiasdepaiva parityattenuatesintraepithelialcornealsensorynervelossinfemalemice