Radioprotective effect of a metalloporphyrin compound in rat eye model.
OBJECTIVE
The purpose of this study was to evaluate the efficacy of the antioxidant Mn (III) tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP) in protecting ocular tissue and retinal microvasculature from radiation damage.


METHODS
75 rats were treated with Mn TE-2-PyP at 2.5 micro g/injection into one eye an hour before proton irradiation. The radiation was delivered in a single fraction to total doses of 8 Gray (Gy) or 28 Gy; Rats were sacrificed 3 days and 3, 6, 9, and 12 months thereafter for histology and quantification of photoreceptor cell populations and retinal capillary changes.


RESULTS
By 6 months following radiation, there was significant loss of retinal outer and inner nuclear layers in eyes receiving radiation only (8 and 28 Gy) (p < 0.05) compared to their controls and to the eyes of rats treated with radiation plus metalloporphyrin. Retinal microvessel length density decreased significantly 6 months following 28 Gy (p < 0.05) compared to their controls and to MnTE-2-PyP treated rats. By 12 months following irradiation, irradiated eyes showed extensive damage to the photoreceptor layer, whereas the eyes of animals receiving radiation plus MnTE-2-PyP showed almost no morphological damage. MnTE-2-PyP treatment also suppressed radiation-induced apoptosis in our study.


CONCLUSIONS
These results demonstrated that MnTE-2-PyP protected both photoreceptors and retinal capillaries from radiation damage, suggesting that this metalloporphyrin antioxidant is effective in regulating the damage induced by proton radiation.
Mao
X W
XW
Department of Radiation Medicine, Molecular Radiation Biology Laboratories, Loma Linda University and Medical Center, Loma Linda, California, USA. xmao@dominion.llumc.edu
Crapo
J D
JD
Mekonnen
T
T
Lindsey
N
N
Martinez
P
P
Gridley
D S
DS
Slater
J M
JM
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002386:Cataract / Q000145:classification / Q000209:etiology / Q000517:prevention & control; D019084:Fluorescent Antibody Technique, Indirect; D007908:Lens, Crystalline / Q000528:radiation effects; D008297:Male; D008665:Metalloporphyrins / Q000627:therapeutic use*; D020419:Photoreceptor Cells, Vertebrate / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects; D011522:Protons; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000528:radiation effects; D012164:Retinal Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D012171:Retinal Vessels / Q000473:pathology / Q000528:radiation effects; D016896:Treatment Outcome
D000975:Antioxidants; D008665:Metalloporphyrins; D011522:Protons; D011837:Radiation-Protective Agents; C431023:manganese (III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin; D053148:Caspase 3