Measuring intraocular antibodies in eyes treated with anti-vascular endothelial growth factor

Rullo, Jacob; Bae, Steven S.; Far, Parsa Mehraban; Hazimi, Amro Al; Gupta, Vasudha; Bal, Manpartap; Hopman, Wilma M.; Irrcher, Isabella; Urton, Todd; Bona, Mark; Campbell, Robert J.; Gonder, Tom; Sharma, Sanjay

doi:10.1016/j.jcjo.2019.11.010

Cited by 2 publications

(1 citation statement)

References 12 publications

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“…RD imposes a significant health burden, as more than 18 million individuals are affected [3]. Thus far, several etiological factors have been shown to be implicated in the pathophysiological mechanism of RD, including oxidative stress, inflammation, and aging-related impairments [4,5]. Due to the disease's complex pathogenic background, the current existing therapeutic methods cannot completely arrest the photoreceptor death in RD.…”

Section: Introductionmentioning

confidence: 99%

Intravitreal Injection of ZYAN1 Restored Autophagy and Alleviated Oxidative Stress in Degenerating Retina via the HIF-1α/BNIP3 Pathway

Hao,

Zhao,

Huang

et al. 2023

Antioxidants

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Mitochondrial autophagy plays a contributary role in the pathogenesis of retina degeneration (RD). ZYAN1 is a novel proline hydroxylase domain (PHD) inhibitor that can enhance the expression of hypoxia-inducible factor 1-alpha (HIF-1α). This study investigated whether ZYAN1 could alleviate progressive photoreceptor loss and oxidative damage in a pharmacologically induced RD model via the modulation of mitophagy. ZYAN1 was injected into the vitreous body of the RD model, and the retinal autophagy level was analyzed. The therapeutic effects of ZYAN1 were evaluated via a function examination, a morphological assay, in situ reactive oxygen species (ROS) detection, and an immunofluorescence assay. It was shown that the thickness of the outer nuclear layer (ONL) increased significantly, and visual function was efficiently preserved via ZYAN1 treatment. The mitochondria structure of photoreceptors was more complete in the ZYAN1-treated mice, and the number of autophagosomes also increased significantly. Membrane disc shedding and ROS overproduction were alleviated after ZYAN1 treatment, and the axonal cilia were more structurally intact. A Western blot analysis showed that the expression levels of the autophagy-related proteins LC3-B, Beclin-1, and ATG5 increased significantly after ZYAN1 treatment, while the expression of P62 was down-regulated. Moreover, the expression levels of HIF-1α and BNIP3 were up-regulated after ZYAN1 treatment. Therefore, an intravitreal injection of ZYAN1 can act as part of the pharmacologic strategy to modulate mitophagy and alleviate oxidative stress in RD. These findings enrich our knowledge of RD pathology and provide insights for the discovery of a therapeutic molecule.

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Section: Introductionmentioning

confidence: 99%

Intravitreal Injection of ZYAN1 Restored Autophagy and Alleviated Oxidative Stress in Degenerating Retina via the HIF-1α/BNIP3 Pathway

Hao,

Zhao,

Huang

et al. 2023

Antioxidants

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Preclinical Observations of Systemic and Ocular Antidrug Antibody Response to Intravitreally Administered Drugs

Wessels

Zadak

Weidmann

et al. 2022

AAPS J

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Intravitreally administered biotherapeutics can elicit local and systemic immune responses with potentially serious clinical consequences. However, little is known about the mechanisms of ocular antidrug immune response, the incidence of ocular antidrug antibodies (ADAs), and the relationship between ocular and systemic ADA levels. Bioanalytical limitations and poor availability of ocular matrices make studies of ocular immunogenicity particularly challenging. We have recently reported a novel bioanalytical ADA assay and shown its applicability for the ADA detection in ocular matrices. In the present study, we used this assay to analyze a large set of preclinical samples from minipig and cynomolgus monkeys treated with different ocular biotherapeutics. We found a significant association between the incidence of ADAs in plasma and ocular fluids after a single intravitreal administration of the drugs. Importantly, none of the animals with ADA-negative results in plasma had detectable ADAs in ocular fluids and systemic ADA response always preceded the appearance of ocular ADAs. Overall, our results suggest the systemic origin of ocular ADAs and support the use of plasma as a surrogate matrix for the detection of ocular ADA response. Graphical Abstract

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Measuring intraocular antibodies in eyes treated with anti-vascular endothelial growth factor

Cited by 2 publications

References 12 publications

Intravitreal Injection of ZYAN1 Restored Autophagy and Alleviated Oxidative Stress in Degenerating Retina via the HIF-1α/BNIP3 Pathway

Intravitreal Injection of ZYAN1 Restored Autophagy and Alleviated Oxidative Stress in Degenerating Retina via the HIF-1α/BNIP3 Pathway

Preclinical Observations of Systemic and Ocular Antidrug Antibody Response to Intravitreally Administered Drugs

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