PAMpeR · Patroller monocytes as modulators of diabetic retinopathy
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-05-16 → 2020-05-15
- EU contribution
- €180,277
- Participants
- 1
- Scheme
- MSCA-IF-EF-SE
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Results in brief
Patroller monocytes as modulators of diabetic retinopathy
Our overall goal is to identify mechanisms efficient in the repair of microvessels in diabetes; as the possibility of measuring, and potentially activating such mechanisms could permit us to develop biomarkers of risk, as well as therapeutics to limit the complications of diabetes (DM). Preliminary data indicate that a discrete subpopulation of circulating monocytes, known as patrolling monocytes (PMo), represents an endogenous mechanism that protects and repairs retinal microvessels against diabetes. In 2010 in Europe, over 3.6 million individuals were affected by DR, and over 500,000 had a severe visual impairment resulting from DM, representing an annual total financial cost to the community of €106,000 per 100,000 inhabitants. Epidemiological data predict a dramatic increase in the prevalence of diabetes in Europe, rising from 55 million in 2010, to over 66 million in 2030. It is reasonable to assume there will be a parallel increase in all its complications, including diabetic retinopathy (DR) the most common complication of DM. In this perspective, it is imperative to develop better means to identify, prevent, and treat DR in its early stages; to develop biomarkers of risk; as well as therapeutics to limit the complications of DM. Notably, the impact and relevance of DR in Europe are such that one of the main goals of IMI 2 - call 1 was to improve and enhance investigation for the discovery of new therapeutic options for DR. The objectives of this project were to: (1) learn whether the biosynthetic profile of PMo changes in relation to increasing duration of diabetes and evolving retinal vascular damage; and, most importantly, (2) bring the study of PMo to clinical investigation. In conlcusion, this project helps us expand our knowledge on the mechanisms through which PMo exert their protective activities in microvessels in an animal model of diabetes, and potentially in humans. in addition, this project helps us generate the concept that microvessels respond to the presence and activity of PMo with a biosynthetic program functional to the restoration of vascular wellbeing. Integration of the human findings with the data generated in animals, has the potential to foster the development of new therapeutic interventions for the prevention, and for the treatment of DR.
Data: CORDIS, © European Union
Project objective
Diabetic retinopathy is the first vascular complication of diabetes and the leading cause of legal blindness among adults in Europe. The fact that diabetic retinopathy is preceded by a long latency period has suggested to us that its natural history could incorporate a phase of vascular repair, active after short duration of diabetes and eventually losing efficacy over time. “Patroller” monocytes, a discrete subpopulation of circulating monocytes, patrol healthy vessels by “crawling” on the endothelium at a speed that is order of magnitude lower than rolling, and at variance with the ""classic"" monocyte subset produce preferentially housekeeping and trophic factors rather than inflammatory cytokines. Our preliminary data strongly support a role of patrollers, in protecting and repairing retinal vessels in diabetes; suggest that the beneficial activities are delivered during leukostasis; and indicate that 5 months of diabetes duration activates a healing/protective transcriptional program in patrollers. I seek to learn whether the biosynthetic profile of patrollers changes in relation to increasing duration of diabetes and evolving retinal vascular damage; and, most importantly, I seek to bring the study of patrollers to clinical investigation. The Objectives are to: 1. Learn if circulating patrollers adapt their biosynthetic profile to different diabetes duration (3 and 9 months) and to the evolving vascular damage 2. Bring the project to clinical applicability by start setting up a human study that aims to compare and contrast the number of circulating patrollers, as well as selected biosynthetic and functional characteristics of these cells, in T1DM patients with no DR after 4-8 years of DM, in T1DM patients with initial nonproliferative DR, and in healthy control subjects. The expectation is to capture from endogenous systems the types of molecular actions that protect the vessels in early diabetes; and thus be enabled to mimic, complement, or leverage""
Original text from CORDIS.
Participants
- OSPEDALE SAN RAFFAELE SRL · MilanoCoordinatorItaly
Links
Data: CORDIS, © European Union