Heping Xu Queen’s University Belfast

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Heping Xu Queen’s University Belfast

Heping Xu

Professor Heping Xu

Professor

  • School of Medicine, Dentistry and Biomedical Sciences – Professor
  • Centre for Experimental Medicine
  • Institute for Health Sciences

Phone: +44 (0)28 9097 6463, +44 (0)28 906 33615

For media contact email comms.office@qub.ac.uk
or call +44(0)2890 973091.

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Interests

 

Research Interests:

Immunology, particularly the immune regulation of autoimmune disease, and inflammation in degenerative and angiogenic diseases.

Retinal diseases, including age-related macular degeneration, diabetic retinopathy and uveoretintis.

For more information about my research please visit Dr Xu’s Laboratory Page.

Please visit GoogleScholar to see the full list of public ations from my group.

Research Statement

I am interested in the cellular and molecular mechanisms involved in sight-theratening retinal diseases, including age-related retinal degeneration, diabetic retinopathy and uveitis. The research questions of my group centre on 1) the initiation and regulation of retinal inflammatory response during ageing and diabetes, 2) autoimmune response in uveitis, 3) the contribution of retinal inflammation to neuroretinal degeneration, and 4) defining the link between chronic retinal inflammation and retinal angiogenesis. The goal is to use this knowledge for designing novel and rational strategies for immunotherapy.

Immunopathogenesis of age-related retinal degenerative disease

Age-related macular degeneration (AMD) is a disease in which the neuroretina, in particular the macular, degenerates with age, resulting in loss of visual function. AMD is the leading cause of blindness in the elderly in developed countries. In the UK, AMD accounts for almost 50% of those registered blind or partially sighted.

Clinically, AMD begins with drusen depositions between retinal pigment epithelial (RPE) cells and choroid at the macular region (so called age-related maculopathy, ARM). The disease can advance into two forms of AMD causing substantial vision loss. The “dry” AMD refers to central geographic atrophy resulting from apoptosis of RPE cells, and subsequently the death of photoreceptor cells in the macular. The “wet” AMD refers to neovascular or exudative AMD. The disease is caused by the retinal ingrowth of abnormal blood vessels from the choroid. Bleeding, leaking and scaring from new vessel damage photoreceptors resulting in rapid vision loss.

AMD is a multifactorial disease. Aging, environmental factors (smoking, diet, sun-light exposure), and certain gene mutations all contribute to the disease development. Exactly, how these multiple factors work together leading to AMD is not known. Based on Herman’s “free radical theory of aging” (Harman. 1956), e hypothesize that age-related retinal degenerative disease is an imbalance between free radical-induced retinal damage and the retinal repairing/remodelling function. The key questions that we are addressing include (1) what are the immune responses in response to free-radical-mediated retinal injury during normal aging? (2) why do such immune responses fail to restore retinal homeostasis in individuals with AMD?

Our studies in normal aging retina have shown that retinal ageing is accompanied with a number of para-inflammatory changes (Xu et al. 2009), including microglial activation (Xu et al. 2009, Chen et al. 2009) and subretinal migration (Xu et al. 2008a, Xu et al. 2009), complement activation at the retinal/choroidal interface (Chen et al. 2008, Xu et al. 2009), and choroidal inflammation (Chen et al. 2008, Xu et al. 2009). In line with the “free radical theory of ageing” significantly more oxidative stress exists in the ageing retina as compared to that in young retina (Xu et al. 2009).

This observation uncovered a common phenomenal i.e. chronic stress (ageing, in this case) induces para-inflammation. In the ageing retina, the innate immune response, i.e. complement activation and microglial activation, constitutes the para-inflammatory response.

Chronic inflammation and retinal angiogenesis

Retinal angiogenesis may occur in different pathological conditions such as retinal premature, diabetic retinopathy, AMD and chronic retinal or choroidal inflammation. Although ischemia has been considered as the key primary stimulator for retinal angiogenesis, accumulating evidence suggests that inflammation may also play important roles, in particular in patients with AMD and chronic choroidal/retinal inflammation. Experimental studies in various retinal angiogenesis models including hypoxia-induce and laser-induced angiogenesis, have shown that inflammatory responses is an important component of retinal angiogenesis. The aim of this part of our study is to uncover the secret underlying the link between chronic inflammation and angiogenesis in neuroretinal tissue.

Inflammation in diabetic retinopathy

Diabetic retinopathy (DR) is the progressive degeneration of retinal vasculature and neurons resulting from diabetes. During diabetes, hyperglycemia and metabolic intermediates are noxious stimuli to tissue cells. The immune system defenses the host against the “danger” stimuli by mounting a pare-inflammatory response. However, compelling evidence suggests that para-inflammation in the DR is disregarded and chronic inflammation contributes to the pathogenesis of DR. We aim to understand how inflammation in DR is dysregulated. Particularly, we are interested in the impact of metabolic disorder on immune cells, the link between inflammation (microglia/complement activation) and retinal neuronal and vascular degeneration.

Novel intraocular drug delivery for inflammatory/angiogenic retinal diseases

Intraocular drug delivery remains the biggest challenge for the management of chronic retinal diseases, such as AMD, DR, and uveoretinitis. In collaboration with scientists in biomaterials and pharmaceutics, and biotechnology industries we are developing a safe and sustained intraocular drug delivery system for the management of retinal inflammatory and angiogenesis diseases.

 

For more detailed information on Dr Xu’s Reserach, please visit ” Dr Xu’s Laboratory Page”.

Other

Editorial Services

2015 – Present: Editorial Board Member of International Journal of Ophthalmic Research.

2015 – Present: Editorial Board Member of Macrophage.

2014 – Present: Editorial Board Member of Scientific Reports.

2013 – Present: Editorial Board of the Scientific World Journal.

2010 – Present: Editorial Board Member of World Journal of Stem Cells (WJSC).