Novel therapies for proliferative retinopathies

Martinez-Alejo, Juan Manuel; Baiza-Durán, Leopoldo Martín; Quintana-Hau, Juan D

doi:10.1177/20406223221140395

Cited by 4 publications

(2 citation statements)

References 62 publications

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“…Therefore, the development of novel HIF-1α inhibitors targeting pathological angiogenesis in ocular diseases is strongly pursued at the preclinical level. In experimental models, for instance, anti-HIF-1α siRNA prior to hypoxia exposure has been shown to decrease HIF-1α and VEGF expression and reduce hypoxia-induced angiogenesis, suggesting that the activated HIF-1α/VEGF pathway is responsible for hypoxia-induced angiogenesis [ 84 ]. In addition, selected compounds inhibiting HIF-1α have been investigated on screening platforms.…”

Section: Management Of Neovascular Retinal Diseasesmentioning

confidence: 99%

Pharmacotherapy and Nutritional Supplements for Neovascular Eye Diseases

Rusciano

Bagnoli

2023

Medicina

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In this review, we aim to provide an overview of the recent findings about the treatment of neovascular retinal diseases. The use of conventional drugs and nutraceuticals endowed with antioxidant and anti-inflammatory properties that may support conventional therapies will be considered, with the final aim of achieving risk reduction (prevention) and outcome improvement (cooperation between treatments) of such sight-threatening proliferative retinopathies. For this purpose, we consider a medicinal product one that contains well-defined compound(s) with proven pharmacological and therapeutic effects, usually given for the treatment of full-blown diseases. Rarely are prescription drugs given for preventive purposes. A dietary supplement refers to a compound (often an extract or a mixture) used in the prevention or co-adjuvant treatment of a given pathology. However, it must be kept in mind that drug–supplement interactions may exist and might affect the efficacy of certain drug treatments. Moreover, the distinction between medicinal products and dietary supplements is not always straightforward. For instance, melatonin is formulated as a medicinal product for the treatment of sleep and behavioral problems; at low doses (usually below 1 mg), it is considered a nutraceutical, while at higher doses, it is sold as a psychotropic drug. Despite their lower status with respect to drugs, increasing evidence supports the notion of the beneficial effects of dietary supplements on proliferative retinopathies, a major cause of vision loss in the elderly. Therefore, we believe that, on a patient-by-patient basis, the administration of nutraceuticals, either alone or in association, could benefit many patients, delaying the progression of their disease and likely improving the efficacy of pharmaceutical drugs.

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Section: Management Of Neovascular Retinal Diseasesmentioning

confidence: 99%

Pharmacotherapy and Nutritional Supplements for Neovascular Eye Diseases

Rusciano

Bagnoli

2023

Medicina

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“…For instance, in the vitreous fluid of patients suffering from neovascular eye disorders, VEGF may be only one of the detectable proangiogenic factors ( Simó et al, 2006 ), which may cause resistance to anti-VEGF therapies. In this respect, novel anti-angiogenic molecules with increased intravitreal residence time to produce long-lasting effects are under development ( Martinez-Alejo et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

A promising case of preclinical-clinical translation: β-adrenoceptor blockade from the oxygen-induced retinopathy model to retinopathy of prematurity

Cammalleri,

Filippi,

Dal Monte

et al. 2024

Front. Physiol.

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Although compartmentalization of the eye seems to promote its experimental manipulation, drug penetration to its posterior part is severely limited by hard barriers thus hindering drug development for eye diseases. In particular, angiogenesis-related retinal diseases share common mechanisms and are responsible for the majority of cases of blindness. Their prevalence is globally increasing mostly because of the increased incidence of systemic pathologies in the adult. Despite the number of preclinical findings demonstrating the efficacy of novel treatments, therapy of retinal neovascular diseases still remains confined to intravitreal anti-vascular endothelial growth factor treatments with some extension to anti-inflammatory therapy. In the mare magnum of preclinical findings aimed to develop novel avenues for future therapies, most compounds, despite their efficacy in experimental models, do not seem to meet the criteria for their therapeutic application. In particular, the groove between preclinical findings and their clinical application increases instead of decreasing and the attempt to bridging the gap between them creates intense frustration and a sense of defeat. In this complex scenario, we will discuss here the role that overactivation of the sympathetic system plays in retinal vessel proliferation in response to hypoxia using the oxygen-induced retinopathy (OIR) model. The potential application of the beta-adrenoceptor (β-AR) blockade with propranolol to the treatment of retinopathy of prematurity will be also discussed in light of preclinical findings in the OIR model and clinical trials using propranolol in preterm infants either per os or as eye drops.

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A TRP to Pathological Angiogenesis and Vascular Normalization

Katari,

Dalal,

Adapala

et al. 2024

Comprehensive Physiology

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Uncontrolled angiogenesis underlies various pathological conditions such as cancer, age‐related macular degeneration (AMD), and proliferative diabetic retinopathy (PDR). Hence, targeting pathological angiogenesis has become a promising strategy for the treatment of cancer and neovascular ocular diseases. However, current pharmacological treatments that target VEGF signaling have met with limited success either due to acquiring resistance against anti‐VEGF therapies with serious side effects including nephrotoxicity and cardiovascular‐related adverse effects in cancer patients or retinal vasculitis and intraocular inflammation after intravitreal injection in patients with AMD or PDR. Therefore, there is an urgent need to develop novel strategies which can control multiple aspects of the pathological microenvironment and regulate the process of abnormal angiogenesis. To this end, vascular normalization has been proposed as an alternative for antiangiogenesis approach; however, these strategies still focus on targeting VEGF or FGF or PDGF which has shown adverse effects. In addition to these growth factors, calcium has been recently implicated as an important modulator of tumor angiogenesis. This article provides an overview on the role of major calcium channels in endothelium, TRP channels, with a special focus on TRPV4 and its downstream signaling pathways in the regulation of pathological angiogenesis and vascular normalization. We also highlight recent findings on the modulation of TRPV4 activity and endothelial phenotypic transformation by tumor microenvironment through Rho/YAP/VEGFR2 mechanotranscriptional pathways. Finally, we provide perspective on endothelial TRPV4 as a novel VEGF alternative therapeutic target for vascular normalization and improved therapy. © 2024 American Physiological Society. Compr Physiol 14:5389‐5406, 2024.

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Novel therapies for proliferative retinopathies

Cited by 4 publications

References 62 publications

Pharmacotherapy and Nutritional Supplements for Neovascular Eye Diseases

Pharmacotherapy and Nutritional Supplements for Neovascular Eye Diseases

A promising case of preclinical-clinical translation: β-adrenoceptor blockade from the oxygen-induced retinopathy model to retinopathy of prematurity

A TRP to Pathological Angiogenesis and Vascular Normalization

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