Diabetic Retinopathy in the Aging Population: A Perspective of Pathogenesis and Treatment

Abstract

The elderly population in the United States is projected to almost double by the year 2050. In addition, the numbers of diabetics are rising, along with its most common complication, diabetic retinopathy (DR). To effectively treat DR within the elderly population, it is essential first to consider the retinal changes that occur due to aging, such as decreased blood flow, retinal thinning, and microglial changes, and understand that these changes can render the retina more vulnerable to oxidative and ischemic damage. Given these considerations, as well as the pathogenesis of DR, specific pathways could play a heightened role in DR progression in elderly patients, such as the polyol pathway and the vascular endothelial growth factor (VEGF) axis. Current ocular treatments include intravitreal corticosteroids, intravitreal anti-VEGF agents, laser photocoagulation and surgical interventions, in addition to better control of underlying diabetes with an expanding range of systemic treatments. While using therapeutics, it is also essential to consider how pharmacokinetics and pharmacodynamics change with aging; oral drug absorption can decrease, and ocular drug metabolism might affect the dosing and delivery methods. Also, elderly patients may more likely be nonadherent to their medication regimen or appointments than younger patients, and undertreatment with anti-VEGF drugs often leads to suboptimal outcomes. With a rising number of elderly DR patients, understanding how aging affects disease progression, pharmacological metabolism, and adherence are crucial to ensuring that this population receives adequate care.

Mechanistic Pathogenesis of Endothelial Dysfunction in Diabetic Nephropathy and Retinopathy

“…PDGF is involved in the embryonic development of many organs, including the brain, lung, retina, vasculature, and kidney, of which the most interesting is the role of PDGF in the vasculature ( 124 – 128 ). PDGFs play an important role in physiological angiogenesis by recruiting vascular endothelial cells, a large number of studies have shown that PDGFs and their receptors play a key role in many ocular neovascular diseases, such as proliferative diabetic retinopathy (PDR), retinopathy of prematurity (ROP), and neovascular age-related macular degeneration (NVAMD) ( 122 , 128 ). Three isoforms of PDGF (AA, AB, and BB) have been shown not only to be involved in the process of neovascularization in PDR, but also to play an important role in the formation of fibrotic tissue in the retina of PDR patients ( 128 ).…”

“…PDGFs play an important role in physiological angiogenesis by recruiting vascular endothelial cells, a large number of studies have shown that PDGFs and their receptors play a key role in many ocular neovascular diseases, such as proliferative diabetic retinopathy (PDR), retinopathy of prematurity (ROP), and neovascular age-related macular degeneration (NVAMD) ( 122 , 128 ). Three isoforms of PDGF (AA, AB, and BB) have been shown not only to be involved in the process of neovascularization in PDR, but also to play an important role in the formation of fibrotic tissue in the retina of PDR patients ( 128 ). The concentration of PDGF-AB in the vitreous humor of patients with diabetic retinopathy is increased, and PDGF-C and PDGF-D are also abundantly expressed in the retina ( 128 ).…”

“…Three isoforms of PDGF (AA, AB, and BB) have been shown not only to be involved in the process of neovascularization in PDR, but also to play an important role in the formation of fibrotic tissue in the retina of PDR patients ( 128 ). The concentration of PDGF-AB in the vitreous humor of patients with diabetic retinopathy is increased, and PDGF-C and PDGF-D are also abundantly expressed in the retina ( 128 ). Recent studies in ocular neovascularization models have shown that simultaneous inhibition of VEGF and PDGF, especially PDGF-B, enhances antiangiogenic effects ( 122 – 125 ).…”

“…PDGFs exert their diverse functions under physiological or pathological conditions by binding to platelet-derived growth factor receptors (PDGFRs) ( 124 , 125 ). PDGF is involved in the embryonic development of many organs, including the brain, lung, retina, vasculature, and kidney, of which the most interesting is the role of PDGF in the vasculature ( 124 – 128 ). PDGFs play an important role in physiological angiogenesis by recruiting vascular endothelial cells, a large number of studies have shown that PDGFs and their receptors play a key role in many ocular neovascular diseases, such as proliferative diabetic retinopathy (PDR), retinopathy of prematurity (ROP), and neovascular age-related macular degeneration (NVAMD) ( 122 , 128 ).…”

miRNA, lncRNA and circRNA: Targeted Molecules Full of Therapeutic Prospects in the Development of Diabetic Retinopathy

“…In the past 30 years, the prevalence of diabetic retinopathy has increased by 7.7%, but the crude prevalence of other blinding diseases has decreased ( 5 ). As a complication of a chronic disease, the prevalence and severity of DR are positively correlated with age and the course of the disease ( 6 ). The relatively long course of DR can be divided into mild DR or nonproliferative DR (NPDR), characterized by an increase in the number of microaneurysms, and proliferative DR (PDR), characterized by the formation of new blood vessels on the posterior surface of the retina and vitreous, which is more severe than NPDR.…”