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Diadenosine tetraphosphate protects sympathetic terminals from 6‐hydroxydopamine‐induced degeneration in the eye
Author(s) -
Hoyle C. H. V.,
Pintor J. J.
Publication year - 2010
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2010.02089.x
Subject(s) - hydroxydopamine , neuroprotection , neurodegeneration , aqueous humour , glaucoma , miosis , medicine , intraocular pressure , ocular hypertension , pharmacology , neuroscience , ophthalmology , biology , parkinson's disease , disease
Aims: To examine diadenosine tetraphosphate (Ap 4 A) for its ability to protect the eye from neurodegeneration induced by subconjunctival application of 6‐hydroxydopamine (6‐OHDA). Methods: Intraocular neurodegeneration of anterior structures was induced by subconjunctival injections of 6‐OHDA. Animals were pre‐treated with topical corneal applications of Ap 4 A or saline. Results: 6‐OHDA caused miosis, abnormal pupillary light reflexes, a precipitous drop in intraocular pressure and loss of VMAT2‐labelled (vesicle monoamine transporter‐2, a marker for sympathetic neurones) intraocular neurones. Pre‐treatment with Ap 4 A prevented all of these changes from being induced by 6‐OHDA, demonstrably preserving the sympathetic innervation of the ciliary processes. This neuroprotective action of Ap 4 A was not shared with the related compounds adenosine, ATP or diadenosine pentaphosphate. P2‐receptor antagonists showed that the effects of Ap 4 A were mediated via a P2‐receptor. Conclusion: Ap4A is a natural component of tears and aqueous humour, and its neuroprotective effect indicates that one of its physiological roles is to maintain neurones within the eye. Ap 4 A can prevent the degeneration of intraocular nerves, and it is suggested that this compound may provide the basis for a therapeutic intervention aimed at preventing or ameliorating the development of glaucoma associated with neurodegenerative diseases. Furthermore, subconjunctival application of 6‐OHDA provides a useful model for studying diseases that cause ocular sympathetic dysautonomia.