Growth hormone and ocular dysfunction: Endocrine, paracrine or autocrine etiologies?
Introduction
It is now more than 10 years since Frystyk considered growth hormone (GH) and insulin-like growth factor (IGF)-1, its classical mediator, as causal factors in the development of diabetic retinopathy (The Growth Hormone Hypothesis — 2005 Revision, [37]). At that time it was thought that this might reflect endocrine actions of pituitary GH within the eye or actions of GH and IGF-1 within the periphery that secondarily induced ocular dysfunction. However, it is now known that GH expression is not restricted to the pituitary gland and that it occurs in ocular tissues, in which autocrine or paracrine actions of GH might contribute to the etiology of ocular dysfunction. These possibilities are the focus of this brief review.
Section snippets
Endocrine etiologies: direct effects of growth hormone
As GH receptors (GHRs) are present in the eye they are target sites of GH produced locally and/or for GH derived from the pituitary gland [56], [57]. The retinopathy associated with GH could thus reflect direct actions of GH on the proliferation of microvascular endothelial cells, which occurs in vitro at physiological concentrations [111] and results in angiogenesis [126]. A causal relationship between pituitary hormones and vision-threatening proliferative diabetic retinopathy (PDR) was first
Endocrine etiologies: indirect effects of growth hormone
The progression of diabetic retinopathy is exacerbated by factors that lead to poor metabolic control. Indeed, the Early Treatment Diabetic Retinopathy Study (ETDRS) identified a number of important factors that decreased visual acuity, including high levels of hemoglobin AIC (HbAIc), decreased hematocrit and increased serum lipids [110]. Hyperglycemia results in an increase in HbAIc and hyperglycemia induces a sequela of biochemical events that result in endothelial proliferation, capillary
Autocrine/paracrine etiologies
In recent years, it has been realized that GH, like other pituitary hormones [51], [52] is widely expressed in many extrapituitary tissues [53]. For instance, it is produced within the CNS, where it has autocrine or paracrine roles in health and disease [50]. Within the CNS, retinal ganglion cells (RGCs) are an established extrapituitary site of GH production [11] and retinal GH has autocrine or paracrine roles in ocular development and vision [56], [57]. Within the retina the control of
Future perspectives
While laser photocoagulation or vitrectomy remain the conventional approach for PDR [130] a number of new treatments have been proposed, particularly those that normalize glycometabolic control [110] or involve the intravitreal injections of steroids, vascular endothelial growth factor inhibitors or angiotensin converting enzyme inhibitors [119]. However, as direct or indirect actions of pituitary GH or autocrine or paracrine actions GH produced in the eye have been implicated in the
Summary
Direct or indirect endocrine actions of pituitary GH (and hepatic IGF-1) or autocrine or paracrine actions of GH (and/or IGF-1) produced within the eye may contribute to ocular dysfunctions including glaucoma and retinopathy. These effects may be direct or reflect the convergent actions of GH in inducing hyperglycemia and hyperlipidemia in the periphery and possibly its augmentation of thrombus formation and induction of von Willebrand factor and endothelial dysfunction leading to retinopathy.
Acknowledgments
Supported by a grant (3617) from the Natural Sciences and Engineering Research Council (NSERC) of Canada and by a postdoctoral fellowship from CONACyT of Mexico to CGMM (238340).
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