Rationale of Basic and Cellular Mechanisms Considered in Updating the Staging System for Diabetic Retinal Disease

IF 3.2 Q1 OPHTHALMOLOGY
M. Elizabeth Hartnett MD , Ward Fickweiler MD, PhD , Anthony P. Adamis MD , Michael Brownlee MD , Arup Das MD, PhD , Elia J. Duh MD , Edward P. Feener PhD , George King MD , Renu Kowluru PhD , Ulrich F.O. Luhmann PhD , Federica Storti PhD , Charles C. Wykoff MD, PhD , Lloyd Paul Aiello MD, PhD , Basic and Cellular Mechanisms Working Group of the Mary Tyler Moore Vision Initiative
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引用次数: 0

Abstract

Purpose

Hyperglycemia is a major risk factor for early lesions of diabetic retinal disease (DRD). Updating the DRD staging system to incorporate relevant basic and cellular mechanisms pertinent to DRD is necessary to better address early disease, disease progression, the use of therapeutic interventions, and treatment effectiveness.

Design

We sought to review preclinical and clinical evidence on basic and cellular mechanisms potentially pertinent to DRD that might eventually be relevant to update the DRD staging system.

Participants

Not applicable.

Methods

The Basic and Cellular Mechanisms Working Group (BCM-WG) of the Mary Tyler Moore Vision Initiative carefully and extensively reviewed available preclinical and clinical evidence through multiple iterations and classified these.

Main Outcome Measures

Classification was made into evidence grids, level of supporting evidence, and anticipated future relevance to DRD.

Results

A total of 40 identified targets based on pathophysiology and other parameters for DRD were grouped into concepts or evaluated as specific candidates. VEGFA, peroxisome proliferator-activated receptor-alpha related pathways, plasma kallikrein, and angiopoietin 2 had strong agreement as promising for use as biomarkers in diagnostic, monitoring, predictive, prognostic, and pharmacodynamic responses as well as for susceptibility/risk biomarkers that could underlie new assessments and eventually be considered within an updated DRD staging system or treatment, based on the evidence and need for research that would fit within a 2-year timeline. The BCM-WG found there was strong reason also to pursue the following important concepts regarding scientific research of DRD acknowledging their regulation by hyperglycemia: inflammatory/cytokines, oxidative signaling, vasoprotection, neuroprotection, mitophagy, and nutrients/microbiome.

Conclusion

Promising targets that might eventually be considered within an updated DRD staging system or treatment were identified. Although the BCM-WG recognizes that at this stage little can be incorporated into a new DRD staging system, numerous potential targets and important concepts deserve continued support and research, as they may eventually serve as biomarkers and/or therapeutic targets with measurable benefits to patients with diabetes.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

更新糖尿病视网膜病变分期系统时考虑的基础和细胞机制原理
目的高血糖是糖尿病视网膜病变(DRD)早期病变的主要风险因素。为了更好地应对早期病变、疾病进展、治疗干预措施的使用以及治疗效果,有必要更新 DRD 分期系统,纳入与 DRD 相关的基础和细胞机制。方法玛丽-泰勒-摩尔视力倡议的基础和细胞机制工作组(BCM-WG)通过多次反复仔细、广泛地审查了现有的临床前和临床证据,并对这些证据进行了分类。结果根据病理生理学和 DRD 的其他参数,共有 40 个已确定的靶点被归类为概念或作为特定候选靶点进行了评估。血管内皮生长因子 (VEGFA)、过氧化物酶体增殖激活受体-α 相关通路、血浆激肽和血管生成素 2 具有很强的一致性,被认为有望用作诊断、监测、预测、预后和药效学反应的生物标志物以及易感性/风险生物标志物,这些生物标志物可作为新评估的基础,并最终在更新的 DRD 分期系统或治疗中得到考虑。BCM-WG 认为有充分理由对 DRD 进行科学研究,并承认高血糖对其的调节作用:炎症/细胞因子、氧化信号、血管保护、神经保护、有丝分裂和营养/微生物组。尽管BCM-WG认识到现阶段几乎没有什么可以纳入新的DRD分期系统,但许多潜在靶点和重要概念值得继续支持和研究,因为它们最终可能成为生物标记物和/或治疗靶点,为糖尿病患者带来可衡量的益处。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Ophthalmology science
Ophthalmology science Ophthalmology
CiteScore
3.40
自引率
0.00%
发文量
0
审稿时长
89 days
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