Anti-neovascular effect of chondrocyte-derived extracellular matrix on corneal alkaline burns in rabbits.
OBJECTIVE
We investigated the effect of a chondrocyte-derived extracellular matrix (CDECM) on experimental corneal alkaline burns in rabbits.


METHODS
Corneal neovascularization (NV) was induced by applying an 8-mm filter paper soaked in 1 N NaOH to the right central corneas of rabbits for 1 minute. Ten days later, the rabbits were randomly divided into three groups: the alkaline burn group, the CDECM transplantation group, and the human amniotic membrane (HAM) transplantation group. The left eyes were used as controls. CDECM and HAM were transplanted onto the corneal surface to completely cover the resected area and were subsequently sutured. On the 10th day after transplantation, the structural changes of the cornea were analyzed histologically. We examined the effects of CDECM on clinical NV features and on the expression of corneal NV markers.


RESULTS
The alkaline burn produced significant NV and increased the corneal thickness. On day 10 after transplantation, the thickness, NV and opacity of the cornea were markedly decreased in the CDECM group (p < 0.001). However, the HAM transplantation group did not exhibit improvements in these clinical parameters, and there were no significant differences relative to the burn group. In addition, the use of CDECM improved the healing of the cornea following the alkaline burn by disrupting the corneal epithelial proliferation and reducing the fibrotic changes of the stroma. The hallmarks of NV were significantly induced in the subepithelium by the alkaline burn, and these levels were also suppressed by CDECM. The CDECM suppressed corneal NV by inhibiting nuclear factor-kappa B (NF-κB) activation by blocking the PKC and Akt signaling pathways.


CONCLUSIONS
CDECM transplantation was markedly effective in healing alkali-burned corneas by modulating the translocation of NF-κB to the nucleus, thereby representing a promising material for the noninvasive treatment of ocular surface disease.
Ocular Neovascular Disease Research Center, Inje University Busan Paik Hospital, Busan, 614-735, Republic of Korea.
Hye Sook
HS
Lee
Ji Hyun
JH
Lee
Chae Eun
CE
Kim
Jae Wook
JW
Yang
D000650:Amnion / Q000637:transplantation; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002057:Burns, Chemical / Q000378:metabolism / Q000628:therapy*; D019902:Chondrocytes / Q000637:transplantation*; D016510:Corneal Neovascularization / Q000378:metabolism / Q000628:therapy*; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000637:transplantation*; D005126:Eye Burns / Q000139:chemically induced*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011817:Rabbits; D012972:Sodium Hydroxide
D015415:Biomarkers; D016328:NF-kappa B; D012972:Sodium Hydroxide; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C