Therapeutic and preventive interventions for postulated vasoactive neuropeptide autoimmune fatigue-related disorders

Staines, Donald

doi:10.1016/j.mehy.2005.03.007

Cited by 6 publications

(1 citation statement)

References 39 publications

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“…Importantly for therapeutic contexts cAMP effects are maintained by phosphodiesterase (PDE) inhibitors which could be used in VN autoimmune disorders. PDE inhibitors have subsets which are highly specific and may constitute appropriately targeted interventions in cAMP disorders [32][33][34]. A case may exist to undertake a therapeutic trial of VN replacement, PDE inhibitors and other agents in autoimmune retinopathies resulting from possible VN autoimmunity.…”

Section: Postulated Vasoactive Neuropeptide Autoimmunity In Retinal Dmentioning

confidence: 99%

Does autoimmunity of endogenous vasoactive neuropeptides cause retinopathy in humans?

Staines

2008

Medical Hypotheses

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Immune privilege is a physiologic mechanism within the eye which protects it against pathogens, while also protecting it from inflammation. Immunological mechanisms in the eye must be tightly regulated to ensure externally mediated injury and infection or internally mediated autoimmunity do not exceed self-defence tolerance. Vasoactive neuropeptides (VNs) including vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase polypeptide (PACAP) and their receptors exist in the mammalian eye including the sclera, cornea, iris, ciliary body, ciliary process and the retina and may have a role in protecting these normally immune privileged sites. VN receptors are class II G protein-coupled receptors (GPCRs) which couple primarily to the adenylate cyclase (AC)-cyclic AMP pathway. A sound blood supply is essential for retinal survival hence vascular compromise will have serious consequences. Retinal vasculitis is a potentially blinding condition with a strong association with systemic inflammatory diseases. Compromise of the endothelial barriers and the blood retina barrier (BRB) may instigate inflammatory responses setting up a chain of events involving VNs in a manner which provokes autoimmunity to them. Protection from BRB breakdown may be linked to nitric oxide (NO) effects and actions of phosphodiesterase inhibitors and cAMP production. Induced NO expressed under influences of inflammatory mediators evokes neurodegeneration and cell apoptosis and may lead to serious ocular disease including retinal injury. Other inflammatory mediators also play a role in retinal pathology. PACAP and glutamate are co-stored in the retinohypothalamic tract and PACAP attenuates glutamate induced neurotoxicity in cultured retinal neurons suggesting that compromise of this VN would have significant detrimental impact on retinal viability though glutamate toxicity. Additional effects of VN compromise would possibly occur through unopposed vasoconstriction and inflammation. Proof of this hypothesis has important implications for treatment and prevention of autoimmune retinopathy and blindness as a number of therapeutic pathways may be opened. Importantly for therapeutic contexts cAMP effects are maintained by phosphodiesterase (PDE) inhibitors which could be used in VN autoimmune disorders. A compelling case may exist to undertake a therapeutic trial of VN replacement, PDE inhibitors and other agents in autoimmune retinopathies resulting from possible VN autoimmunity.

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Section: Postulated Vasoactive Neuropeptide Autoimmunity In Retinal Dmentioning

confidence: 99%

Does autoimmunity of endogenous vasoactive neuropeptides cause retinopathy in humans?

Staines

2008

Medical Hypotheses

Self Cite

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Does dysregulation of key epigenetic and biochemical pathways occur in postulated vasoactive neuropeptide autoimmune disorders?

Staines¹

2005

Medical Hypotheses

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Is Parkinson’s disease an autoimmune disorder of endogenous vasoactive neuropeptides?

Staines

2007

Medical Hypotheses

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Therapeutic and preventive interventions for postulated vasoactive neuropeptide autoimmune fatigue-related disorders

Cited by 6 publications

References 39 publications

Does autoimmunity of endogenous vasoactive neuropeptides cause retinopathy in humans?

Does autoimmunity of endogenous vasoactive neuropeptides cause retinopathy in humans?

Does dysregulation of key epigenetic and biochemical pathways occur in postulated vasoactive neuropeptide autoimmune disorders?

Is Parkinson’s disease an autoimmune disorder of endogenous vasoactive neuropeptides?

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