Inhibition of conjunctival transdifferentiation by topical retinoids.
During the healing of a total corneal epithelial defect extending beyond the limbus, conjunctival transdifferentiation can be inhibited by corneal vascularization as evidenced by the lack of morphological transformation of the conjunctival epithelium into a cornea-like epithelium and the persistence of goblet cells on the corneal surface. We speculated that corneal vascularization might play a causative role in inhibiting conjunctival transdifferentiation, and examined the hypothesis that vitamin A or retinoids might be one of the blood-borne factors in modulating this process. To test this hypothesis, we created total corneal epithelial defects extending 3 mm beyond the limbus in rabbits using n-heptanol, and segregated the resultant corneas into nonvascularized and vascularized groups. After re-epithelialization, both groups received topical 0.1% Etretinate (Roche-Hoffmann, Nutley, NJ) or 13-cis retinoic acid in corn oil three times a day for 8 weeks. Controls received corn oil only. The extent of transdifferentiation was analyzed by assaying goblet cell density and distribution using flat-mount preparations and Alcian blue and periodic acid-Schiff stains (Fischer Scientific Co., Fair Lawn, NJ) and by conventional histology. Topical retinoid application inhibited conjunctival transdifferentiation in nonvascularized corneas to the same extent as that caused by corneal vascularization, suggesting that vitamin A is an important blood-borne factor for goblet cell maintenance. Its relative deficiency in the normal avascular cornea may explain why conjunctival transdifferentiation occurs.
Tseng
S C
SC
Hirst
L W
LW
Farazdaghi
M
M
Green
W R
WR
D000287:Administration, Topical; D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D003228:Conjunctiva / Q000166:cytology*; D003315:Cornea / Q000098:blood supply; D005050:Etretinate / Q000494:pharmacology*; D015474:Isotretinoin; D011817:Rabbits; D014212:Tretinoin / Q000494:pharmacology*
D014212:Tretinoin; D005050:Etretinate; D015474:Isotretinoin