Elsevier

Growth Hormone & IGF Research

Volume 29, August 2016, Pages 28-32
Growth Hormone & IGF Research

Growth hormone and ocular dysfunction: Endocrine, paracrine or autocrine etiologies?

https://doi.org/10.1016/j.ghir.2016.03.004Get rights and content

Highlights

  • The eye is a target site for GH and IGF-I action.

  • GH and IGF-I have been implicated in retinopathy and other ocular dysfunctions.

  • Ocular dysfunction could reflect local or pituitary GH and IGF-I excess.

Abstract

The eye is a target site for GH action and growth hormone has been implicated in diabetic retinopathy and other ocular dysfunctions. However, while this could reflect the hypersecretion of pituitary GH, the expression of the GH gene is now known to occur in ocular tissues and it could thus also reflect excess GH production within the eye itself. The possibility that ocular dysfunctions might arise from endocrine, autocrine or paracrine etiologies of GH overexpression is therefore the focus of this brief review.

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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