Synthetic neurotensin analogues are nontoxic analgesics for the rabbit cornea.
OBJECTIVE
To characterize the analgesic potency and toxicity of topical synthetic neurotensin analogues, and localize neurotensin receptors in the cornea and trigeminal ganglion.


METHODS
Cochet-Bonnet esthesiometry was performed on the rabbit cornea to test the analgesic dose response and duration of effect for two synthetic neurotensin analogues: NT71 and NT72. Receptors for neurotensin were localized in the murine cornea and trigeminal ganglion using quantitative PCR (qPCR), Western blotting, and immunohistochemistry. In vitro toxicity of NT71, NT72, and sodium channel blockers was evaluated using cytotoxicity, single-cell migration, and scratch closure assays performed on rabbit corneal epithelial cells. In vivo toxicity of these agents was assessed using a rabbit laser phototherapeutic keratectomy (PTK) model and histology.


RESULTS
NT71 and NT72 induced potent analgesic effects on the rabbit cornea at concentrations between 1.0 and 2.5 mg/mL, lasting up to 180 minutes. A site-specific distribution of neurotensin receptors was observed in the murine cornea and trigeminal ganglion. NT71 and NT72 did not cause any significant in vitro or in vivo toxicity, in contrast to sodium channel blockers.


CONCLUSIONS
Synthetic neurotensin analogues are potent analgesics that avoid the toxicities associated with established topical analgesic agents. Receptors for neurotensin are present in both the cornea and trigeminal ganglion.
Margaret M. Dyson Vision Research Institute, Department of Ophthalmology, Weill Cornell Medical College, New York, New York, United States.
Charles
C
Kim
Sarentis Therapeutics, Inc., New York, New York, United States.
Denise
D
Barbut
Department of Ophthalmology, Memorial Sloan Kettering Cancer Center, New York, New York, United States.
Murk H
MH
Heinemann
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York, United States.
Gavril
G
Pasternak
Margaret M. Dyson Vision Research Institute, Department of Ophthalmology, Weill Cornell Medical College, New York, New York, United States.
Mark I
MI
Rosenblatt
D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D001767:Blinking / Q000187:drug effects; D015153:Blotting, Western; D002465:Cell Movement; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000187:drug effects* / Q000473:pathology; D065306:Corneal Injuries; D004195:Disease Models, Animal; D005131:Eye Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D009496:Neurotensin / Q000031:analogs & derivatives*; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D018028:Receptors, Neurotensin / Q000096:biosynthesis* / Q000235:genetics; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014945:Wound Healing
D000700:Analgesics; D009883:Ophthalmic Solutions; D012333:RNA, Messenger; D018028:Receptors, Neurotensin; D009496:Neurotensin
corneal wound healing; neurotensin; peptides; topical analgesia