Age-Related Decline in VIP-Positive Parasympathetic Nerve Fibers in the Human Submacular Choroid

Jablonski, Monica M.; Iannaccone, Alessandro; Reynolds, Drew; Gallaher, Preston; Allen, Shaun; Wang, Xiaofei; Reiner, Anton

doi:10.1167/iovs.06-0972

Cited by 33 publications

(28 citation statements)

References 53 publications

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“…In addition, we have shown that vasoactive intestinal polypeptide (VIP)-positive submacular choroidal nerve fi bers from human donor eyes decline with age (Jablonski et al 2007 ) and that, while donor eyes age 70-94 have, on average, 8.8% blood vessel VIP fi ber coverage, early AMD has 1.6% coverage, and advanced AMD has about 0.5% fi ber coverage (unpublished observation). VIP is both a potent vasodilator and a key local anti-infl ammatory and immunomodulatory agent (Gonzalez-Rey and Delgado 2005 ;Pozo et al 2007 ;Smalley et al 2009 ) .…”

Section: Preliminary Results From Our Research Support the Role Of Aumentioning

confidence: 96%

Autoimmune Biomarkers in Age-Related Macular Degeneration: A Possible Role Player in Disease Development and Progression

Iannaccone

Neeli

Krishnamurthy

et al. 2011

Advances in Experimental Medicine and Biology

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Section: Preliminary Results From Our Research Support the Role Of Aumentioning

confidence: 96%

Autoimmune Biomarkers in Age-Related Macular Degeneration: A Possible Role Player in Disease Development and Progression

Iannaccone

Neeli

Krishnamurthy

et al. 2011

Advances in Experimental Medicine and Biology

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“…These changes are also occurring in the context of reduced regulatory potential from the central nervous system–decreased parasympathetic innervation of the choroid has been described in aging in both pigeons (Fitzgerald et al, 2005) and man (Jablonski et al, 2007). Although we believe the most pronounced changes are occurring at the level of the microvasculature of the choroid, pathology of large vessels has also been suggested based on measurements of scleral rigidity, with increased resistance in the vortex veins, reflux and damage to the choriocapillaris and, ultimately, RPE atrophy (Friedman et al, 1989).…”

Section: Model For Amd Pathogenesismentioning

confidence: 99%

“…The innervation of the choroid includes roles for neurons that terminate on large vessel walls and that deliver the potent vasodilator nitric oxide (Li et al, 2010) as well as those without obvious innervation of vascular elements. The role of innervation in maintaining a healthy choroid is an important and active area of study (Fitzgerald et al, 2005; Jablonski et al, 2007; Li et al, 2010; Nickla and Wallman, 2010). …”

Section: Overview Of Choroidal Structure and Functionmentioning

confidence: 99%

Complement activation and choriocapillaris loss in early AMD: Implications for pathophysiology and therapy

Whitmore

Sohn

Chirco

et al. 2015

Progress in Retinal and Eye Research

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Age-related macular degeneration (AMD) is a common and devastating disease that can result in severe visual dysfunction. Over the last decade, great progress has been made in identifying genetic variants that contribute to AMD, many of which lie in genes involved in the complement cascade. In this review we discuss the significance of complement activation in AMD, particularly with respect to the formation of the membrane attack complex in the aging choriocapillaris. We review the clinical, histological and biochemical data that indicate that vascular loss in the choroid occurs very early in the pathogenesis of AMD, and discuss the potential impact of vascular dropout on the retinal pigment epithelium, Bruch's membrane and the photoreceptor cells. Finally, we present a hypothesis for the pathogenesis of early AMD and consider the implications of this model on the development of new therapies.

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“…Aging is also associated with a decrease in lean body mass and a relative increase in fat mass, and it has been suggested to result in a slow progressive redistribution of fat from subcutaneous tissue to central abdominal tissue (Borkan et al 1983;Barbieri et al 2001). Aging is also associated with a generalized reduction in parasympathetic nerve function demonstrated for the cardiovascular system (O'Brien et al 1986;Ingall et al 1990;Corbett et al 2007), eyes (Fitzgerald et al 2005;Tewari et al 2006;Jablonski et al 2007), GI tract (Phillips and Powley 2001, 2007, and urinary bladder (Schneider et al 2005). Parasympathetic dysfunction can be identified before development of diabetes (Lautt 1980), is later associated with the metabolic syndrome (Britton et al 2007) and obesity (Skrapari et al 2007;von Känel et al 2007), but improves with reduced adiposity (Mager et al 2006).…”

mentioning

confidence: 99%

Attenuation of age- and sucrose-induced insulin resistance and syndrome X by a synergistic antioxidant cocktail: the AMIS syndrome and HISS hypothesisThis article is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.

Lautt

Ming

Légaré

2010

Can. J. Physiol. Pharmacol.

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Absence of meal-induced insulin sensitization (AMIS) results in a predictable progression of dysfunctions, including postprandial hyperglycemia, compensatory hyperinsulinemia, resultant hyperlipidemia, increased oxidative stress, and obesity, progressing to syndrome X and diabetes. To one year of age, rats show a slow development of AMIS, but this can be potentiated by addition of a low-dose sucrose supplement to the diet. Provision of a synergistic antioxidant cocktail consisting of S-adenosylmethionine, vitamin E, and vitamin C (Samec) attenuates the rate and extent of development of AMIS in both normal aging animals and in aging animals on the sucrose diet. Adiposity, assessed from weighed regional fat masses and from bioelectrical impedance to estimate whole-body adiposity, correlated strongly with AMIS (r 2 = 0.7-0.8). Rats given the sucrose supplement had accelerated AMIS and developed fasting hyperinsulinemia and postprandial hyperglycemia, hyperlipidemia, hyperinsulinemia, and adiposity. Samec completely compensated for the negative impact of this sucrose supplement and attenuated development of the associated dysfunctions. AMIS is explained by the HISS (hepatic insulin-sensitizing substance) hypothesis, which is outlined in the paper. KeywordsHISS; AMIS; MIS; cardiometabolic risk; preventative; obesity; adiposity; diabetes; Samec This paper was presented at the Canadian Oxidative Stress Consortium meeting held in Winnipeg in May 2009. The central message of the talk was that hepatic insulin-sensitizing substance (HISS)-dependent insulin resistance (HDIR) results in absence of meal-induced insulin sensitization (AMIS) and leads to progressive and predictable homeostatic dysfunctions. AMIS, if chronic, results in the AMIS syndrome. A second message was that the control of meal-induced insulin sensitization (MIS) by 2 feeding signals allows for pharmaceutical restoration of MIS in diabetic models as a first-in-kind therapeutic treatment for prediabetic insulin resistance, syndrome X, and obesity. This paper is based on 3 recent publications that used a synergistic antioxidant cocktail as a research tool to test the AMIS syndrome and HISS hypothesis. CIHR Author Manuscript CIHR Author Manuscript CIHR Author ManuscriptThe HISS hypothesis After a meal, the dynamic glucose disposal response to insulin is increased by at least 100%. In the fed state, a pulse of insulin will result in the release of a pulse of HISS from the liver (Fig. 1). HISS action is selective for skeletal muscle and leads to uptake and storage of glucose as glycogen in the large skeletal muscle mass. HISS release in response to insulin occurs only in the presence of 2 permissive feeding signals, the first being a hepatic parasympathetic-mediated signal (reviewed by Lautt 2004) and the second being a 30%-50% elevation in hepatic glutathione (GSH) levels (Guarino For MIS to be quantified, an index of insulin sensitivity must be used that can be obtained in both the fed and fasted state. MIS has been shown by using changes in arteriov...

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Age-Related Decline in VIP-Positive Parasympathetic Nerve Fibers in the Human Submacular Choroid

Cited by 33 publications

References 53 publications

Autoimmune Biomarkers in Age-Related Macular Degeneration: A Possible Role Player in Disease Development and Progression

Autoimmune Biomarkers in Age-Related Macular Degeneration: A Possible Role Player in Disease Development and Progression

Complement activation and choriocapillaris loss in early AMD: Implications for pathophysiology and therapy

Attenuation of age- and sucrose-induced insulin resistance and syndrome X by a synergistic antioxidant cocktail: the AMIS syndrome and HISS hypothesisThis article is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.

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