Intraocular microinjections repair experimental Parkinson's disease.
Circadian involvement in Parkinson's disease (PD) and more specifically in nigro-striatal dopamine (NSD) function is of increasing interest to the neurosciences. Given that bright light therapy is of therapeutic value in PD, possible mechanisms underlying retinal involvement in this phenomenon was explored further by administering anti-Parkinsonian chemotherapies into the vitreus humour directly adjacent to the retina. 2 microl of a 100 mM solution of L-Dopa significantly improved motor function in the later stages of degeneration and during the day while the injection of 2 microl of a 10 mM solution of the melatonin receptor antagonist ML-23 improved motor function in the early stages of PD and during the dark phase of the light/dark cycle. The results suggest that the function of nigral cells is regulated by a more global system embracing circadian physiology that extends from the retina to the pineal. Furthermore, the induction of PD is characterised by an imbalance between melatonin and dopamine (DA) whereby this ratio is elevated at least 6 to 1 in favour of melatonin. The commonly observed treatment failures and side effects of DA replacement therapy probably result from increasing endogenous DA without taking parallel melatonin dysfunction into account. The proposed integrated function of the NSD and circadian systems may permit therapeutic targeting at a level which is safer, more effective and without the side effects of systemically administered regimens of DA replacement.
Willis
Gregory L
GL
The Bronowski Institute of Behavioural Neuroscience, Coliban Medical Centre, Kyneton, Victoria, Australia. gwillbro@bigpond.com
D008735:5-Methoxytryptamine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage*; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D007980:Levodopa / Q000008:administration & dosage; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects*
D000978:Antiparkinson Agents; C053008:ML 23; D008735:5-Methoxytryptamine; D007980:Levodopa