TY - JOUR
T1 - Topical application of naltrexone facilitates reepithelialization of the cornea in diabetic rabbits
AU - Zagon, I. S.
AU - Sassani, Joseph W.
AU - Carroll, Melissa A.
AU - McLaughlin, Patricia J.
N1 - Funding Information:
This work was supported by NIH grant EY01666 (ISZ) . The authors want to acknowledge the technical help of Ms. Cara Keiper.
PY - 2010/2/15
Y1 - 2010/2/15
N2 - Delayed corneal reepithelialization is a complication of diabetes, and may lead to ulcers and erosions, which cause ocular morbidity and visual loss. This study examined the efficacy of naltrexone (NTX), a long-acting, potent opioid antagonist, applied topically, to facilitate the repair of standardized corneal abrasions in diabetic (alloxan-induced) New Zealand White rabbits (glucose levels > 450 mg/dL). NTX at a concentration of 10-4 M, or sterile vehicle (SV), was administered topically 4 times per day for 7 days to the abraded eye of uncontrolled Type 1 diabetic (DB), insulin-controlled Type 1 diabetic (DB-IN), or non-diabetic (Normal) rabbits. Wound healing was monitored, and non-invasive (tonopen, pachymeter, hand-held slit lamp, and retinal camera) and invasive (histopathology) measurements evaluated. Corneal reepithelialization in the uncontrolled DB rabbits was significantly enhanced (up to a 47% reduction in wound area) following treatment with NTX relative to both Normal SV and DB SV rabbits at 24, 48, and 56 h following surgery. At 72 h, DB NTX rabbits had residual defects that were 64-82% smaller than Normal and DB SV animals. NTX treated DB-IN rabbits had residual defects that were 9-37% smaller than DB-IN rabbits receiving SV, and 6-40% smaller than Normal rabbits. No signs of toxicity from topical applications were noted. These data confirm and extend those documented in rats that demonstrated a lack of toxicity of NTX at a wide range of dosages, as well as efficacy for enhanced corneal epithelialization. These studies set the stage for clinical trials using NTX as a therapy for diabetic keratopathy.
AB - Delayed corneal reepithelialization is a complication of diabetes, and may lead to ulcers and erosions, which cause ocular morbidity and visual loss. This study examined the efficacy of naltrexone (NTX), a long-acting, potent opioid antagonist, applied topically, to facilitate the repair of standardized corneal abrasions in diabetic (alloxan-induced) New Zealand White rabbits (glucose levels > 450 mg/dL). NTX at a concentration of 10-4 M, or sterile vehicle (SV), was administered topically 4 times per day for 7 days to the abraded eye of uncontrolled Type 1 diabetic (DB), insulin-controlled Type 1 diabetic (DB-IN), or non-diabetic (Normal) rabbits. Wound healing was monitored, and non-invasive (tonopen, pachymeter, hand-held slit lamp, and retinal camera) and invasive (histopathology) measurements evaluated. Corneal reepithelialization in the uncontrolled DB rabbits was significantly enhanced (up to a 47% reduction in wound area) following treatment with NTX relative to both Normal SV and DB SV rabbits at 24, 48, and 56 h following surgery. At 72 h, DB NTX rabbits had residual defects that were 64-82% smaller than Normal and DB SV animals. NTX treated DB-IN rabbits had residual defects that were 9-37% smaller than DB-IN rabbits receiving SV, and 6-40% smaller than Normal rabbits. No signs of toxicity from topical applications were noted. These data confirm and extend those documented in rats that demonstrated a lack of toxicity of NTX at a wide range of dosages, as well as efficacy for enhanced corneal epithelialization. These studies set the stage for clinical trials using NTX as a therapy for diabetic keratopathy.
UR - http://www.scopus.com/inward/record.url?scp=73149106360&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=73149106360&partnerID=8YFLogxK
U2 - 10.1016/j.brainresbull.2009.10.009
DO - 10.1016/j.brainresbull.2009.10.009
M3 - Article
C2 - 19853024
AN - SCOPUS:73149106360
SN - 0361-9230
VL - 81
SP - 248
EP - 255
JO - Brain Research Bulletin
JF - Brain Research Bulletin
IS - 2-3
ER -