Abstract
Purpose: :
CD36 is expressed on macrophages and dendritic cells and is best known as the receptor for thrombospondin (TSP–1). TSP–1 triggering of CD36 is known to be involved in TGF–ß activation, angiogenesis, and regulation of protease activity. However, CD36 also functions in a variety of TSP–1 independent functions that are triggered when CD36 binds: apoptotic cells, collagen, and long–chain fatty acids. Thus, the CD36 receptor functions as a multi–ligand scavenger receptor. The following experiments were performed to differentiate between the TSP–1 dependent and independent functions of CD36 during corneal epithelial wound healing.
Methods: :
A 1.5 mm epithelial wound was created in the central cornea without disrupting the epithelial basement membrane using a trephine and blunt scalpel in either CD36 or TSP–1 C57BL/6 null mice. Wild–type C57BL/6 mice were used as a negative control. Wound healing was observed via: (i) fluorescein staining, (ii) slit lamp examination (every other day), and (iii) histological examination at various time points (4, 24, 48, 72, 96 hrs and day 34).
Results: :
If corneal wound healing is the same in TSP–1 null and CD36 null mice, then CD36 is acting mainly as a receptor for TSP–1. However, if wound healing is not the same in these null mice, then CD36 displays TSP–1 independent functions. Wild–type mice displayed normal wound healing in which the cornea was re–epithelialized within 48 hrs and remained clear. By contrast, TSP–1 and CD36 null mice displayed slower re–epithelialization that required up to 4–6 days. TSP–1 null mice developed a diffuse infiltrate in the cornea that resolved by day 6–8 and the cornea remained clear. By contrast, CD36 null mice developed a persistent infiltration that never cleared and resulted in a scar. Histological examination of these lesions revealed a progressive increase in PMN infiltration in the stroma of CD36 null mice.
Conclusions: :
We conclude that corneal scarring is prevented by TSP–1 independent functions of CD36. This predicts that CD36 macrophages may prevent scarring by CD36 dependent phagocytosis of apoptotic cells in the corneal stroma.
Keywords: cornea: stroma and keratocytes • cornea: epithelium • wound healing