Exorbital Lacrimal Gland Ablation and Regrafting Induce Inflammation but Not Regeneration or Dry Eye

Int J Mol Sci. 2024 Jul 30;25(15):8318. doi: 10.3390/ijms25158318.

Abstract

The study evaluated the regenerative responses of the lacrimal functional unit (LFU) after lacrimal gland (LG) ablation. The LG of Wistar rats was submitted to G1) partial LG ablation, G2) partial ablation and transplantation of an allogeneic LG, or G3) total LG ablation, (n = 7-10/group). The eye wipe test, slit lamp image, tear flow, and histology were evaluated. RT-PCR analyzed inflammatory and proliferation mediators. The findings were compared to naïve controls after 1 and 2 months (M1 and M2). G3 presented increased corneal sensitivity, and the 3 groups showed corneal neovascularization. Histology revealed changes in the LG and corneal inflammation. In the LG, there was an increase in MMP-9 mRNA of G1 and G2 at M1 and M2, in RUNX-1 at M1 and M2 in G1, in RUNX-3 mRNA at M1 in G1, and at M2 in G2. TNF-α mRNA rose in the corneas of G1 and G2 at M2. There was an increase in the IL-1β mRNA in the trigeminal ganglion of G1 at M1. Without changes in tear flow or evidence of LG regeneration, LG ablation and grafting are unreliable models for dry eye or LG repair in rats. The surgical manipulation extended inflammation to the LFU.

Keywords: inflammation; lacrimal functional unit; regeneration.

MeSH terms

  • Animals
  • Cornea / metabolism
  • Cornea / pathology
  • Disease Models, Animal
  • Dry Eye Syndromes* / etiology
  • Dry Eye Syndromes* / metabolism
  • Dry Eye Syndromes* / pathology
  • Inflammation* / metabolism
  • Inflammation* / pathology
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Lacrimal Apparatus* / metabolism
  • Lacrimal Apparatus* / pathology
  • Lacrimal Apparatus* / surgery
  • Male
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Rats
  • Rats, Wistar*
  • Regeneration*
  • Tears / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Matrix Metalloproteinase 9
  • Tumor Necrosis Factor-alpha
  • Interleukin-1beta