1: Brain Res. 2008 Jun 27;1217:119-31. Epub 2008 Apr 11.

Intraocular microinjections repair experimental Parkinson's disease.

Willis GL.

The Bronowski Institute of Behavioural Neuroscience, Coliban Medical Centre,
Kyneton, Victoria, Australia. gwillbro@bigpond.com

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.


PMID: 18502399 [PubMed - indexed for MEDLINE]