Survival of Monocytes Collected From Patients With Atrophic AMD in Retinal Pigmented Epithelium Explants

Summary

Age-related macular degeneration (AMD) affects 2 million people in France and is the main cause of irreversible blindness in France. All patients initially have an early form of the disease. This early form can evolve in two different ways: the atrophic form, which progresses slowly, and the exudative or neovascular form, which has a more rapid evolution. While there are treatments for the exudative form of the disease, there is currently no therapy for the atrophic form of AMD. Recently, it has been demonstrated in atrophic AMD that there is accumulation of inflammatory cells, monocytes, in the sub-retinal space. This space is located between the retinal pigment epithelium (RPE) and photoreceptors. It is physiologically devoid of immune cells (immune privilege). Monocytes secrete many pro-inflammatory molecules, such as cytokines. Some cytokines (IL-1, IL6 and TNF) have a deleterious role on RPE and photoreceptors in mouse models. The identification of specific cytokines would help to better understand this disease and consider potential targeted therapies. Our project is based on the hypothesis that monocytes extracted from patients with AMD have a superior survival on RPE compared to monocytes extracted from healthy patients (without retinal pathology), and more particularly in atrophic forms of AMD. The main aim of this study is to compare the survival of monocytes extracted from patients with atrophic AMD to monocytes extracted from patients without retinal pathology (control) on retinal pigment epithelial cell lines (ARPE-19). Survival will be evaluated by automated counting of monocytes after 24 hours of culture on ARPE-19 after specific immunostaining of monocytes. If the survival of monocytes from patients with the late form of AMD is increased then therapy directly targeting this pathological accumulation of monocytes could be considered. Moreover, the identification of increased secretion of certain cytokines and the demonstration of their deleterious effect on retinal physiology could lead to targeted therapies against them.

Conditions

• Age Related Macular Degeneration

Interventions

OTHER

Blood samples

: The blood sample from all groups will be taken on the day of inclusion, in the ophthalmology department. The patient will be cared for by a nurse and then taken to the collection room. A 100 ml sample will be taken (10 tubes of 10 ml). Blood samples will be labeled with the patient's identification number as part of the protocol. They will be transported to the research laboratory in order to be picked up for monocyte extraction. The purification of blood monocytes will be done. In case of excess, the samples will be destroyed at the end of the study.

Sponsors & Collaborators

• Hospices Civils de Lyon

  lead OTHER

Principal Investigators

• Thibaud Mathis, MD · Service d'Ophtalmologie Hospices Civils de Lyon Hôpital de la Croix Rousse

Study Design

Allocation

NON_RANDOMIZED

Purpose

HEALTH_SERVICES_RESEARCH

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

15 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-06-01

Primary Completion

2025-12-02

Completion

2025-12-02

Countries

• France

Study Locations