Vitamin B6 protects primate retinal neurons from ischemic injury.
Vitamin B6 derivatives protect the retinal neurons from excitotoxic injury in vitro. However, their in vivo role in a process involving excitotoxicity, such as ischemia, remains unknown. We studied potential protective effects of pyridoxal 5'-phosphate (PLP) and pyridoxal hydrochloride (pyridoxal) on the retinal neurons in a monkey model of transient global ischemia. Daily intravenous injections (15 mg/kg) of pyridoxal and PLP were performed for consecutive 10 days. On the sixth day, whole brain complete ischemia was produced by clipping the innominate and the left subclavian arteries for 20 min. The monkeys were sacrificed 5 days after ischemia and their retinas were processed for histological analysis. The ischemia induced a marked cellular injury in the retina as shown by the loss of ganglion cells and the reduction of thickness of the ganglion cell, inner plexiform, and inner nuclear layers. PLP significantly prevented the ganglion cell loss and the reduction of thickness of the ganglion cell layer. Pyridoxal significantly prevented the ganglion cell loss as well as the reduction of thickness of ganglion cell, inner plexiform and inner nuclear layers. These results suggest that PLP and pyridoxal counteract the postischemic neuronal death in the adult primate retina, offering a potential for a novel pharmacotherapy of retinal ischemic injury.
Wang
Xiang-Di
XD
Department of Neurosurgery, Division of Neuroscience, Graduate School of Medical Science, Kanazawa University, Takaramachi 13-1, 920-8641, Kanazawa, Japan.
Kashii
Satoshi
S
Zhao
Liang
L
Tonchev
Anton B
AB
Katsuki
Hiroshi
H
Akaike
Akinori
A
Honda
Yoshihito
Y
Yamashita
Junkoh
J
Yamashima
Tetsumori
T
D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D002546:Ischemic Attack, Transient / Q000150:complications / Q000188:drug therapy*; D008251:Macaca; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D009900:Optic Nerve / Q000187:drug effects / Q000473:pathology; D011730:Pyridoxal / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000494:pharmacology; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D012164:Retinal Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D025101:Vitamin B 6 / Q000494:pharmacology*
D011730:Pyridoxal; D011732:Pyridoxal Phosphate; D025101:Vitamin B 6