Advanced Glycation End Products as a Biomarker for Accelerated Ageing

Advanced Glycation End Products as a Biomarker for Accelerated Ageing in Glaucomatous Optic Neuropathy

Globally primary open angle glaucoma (POAG) affects over 60 million people. The exact pathogenesis of POAG is poorly understood. A significant risk factor for glaucoma is advancing age. The rate of ageing is not the same in all age matched individuals. The concept of accelerated ageing suggests that the presence of a number of specific genetic, environmental or systemic risk factors may cumulate to accelerate the ageing process in some individuals and lead to the development of age-related disease. Understanding the factors that influence accelerated ageing is vital.

Advanced glycation end products (AGEs) are a complex group of compounds that are naturally formed. They accumulate gradually with age in cells, tissues and blood vessels throughout the body where they adversely affect structure and function. Circulating AGE levels can be influenced by oxidative stress levels and dietary intake. Recent research has found that sustained exposure to high levels of circulating AGEs could be a major factor in the development of a number of chronic age-related degenerative disorders, including POAG.

To date there have been few clinical studies that have been able to non-invasively explore the association between AGE levels and the development and progression of glaucomatous optic neuropathy (GON), or to explore the possible contribution that oxidative stress and dietary intake make to total tissue AGE levels in such patients. Furthermore little is understood about the relationship between AGE levels and retinal vascular function, a parameter known to be altered in GON that also could be influenced by AGE levels.

The proposed study will aim to evaluate whether tissue-bound AGE levels are associated with parameters of retinal vascular function, oxidative stress, dietary intake and the presence of GON. Establishing this association could increase our understanding of the pathogenesis of GON and allow a new biomarker for accelerated ocular ageing to be realised

Study Overview

• Status: Completed
• Conditions: Primary Open Angle Glaucoma; Ocular Hypertension; Normal Tension Glaucoma

• Study Type: Observational
• Enrollment (Actual): 131

Contacts and Locations

Study Locations

• United Kingdom
  • Devon
    • Plymouth, Devon, United Kingdom, PL4 8AA
      • Plymouth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Healthy controls, ocular hypertension, primary open angle glaucoma and normal tension glaucoma groups aged 50 years and older will be studied. Different parameters will be looked at with an aim to understand ageing in glaucomatous optic neuropathy.

Description

Inclusion Criteria:

• Must have had an eye test within the last two years
• Aged 50+
• Informed, written consent
• Have adequate understanding of English language to be able to comprehend the oral and written instructions.
• Participants must be able to complete a 12-hour overnight fast, which includes no alcohol or caffeine.

Inclusion criteria for Ocular hypertension, Primary open angle glaucoma and normal tension glaucoma:

- Follows guidelines set out within the protocol and used at Derriford REI

Exclusion Criteria:

• Diabetes
• Current smokers
• History of stroke/TIA
• Coronary artery disease/heart failure/arrhythmia/angina
• Peripheral vascular disease
• Severe dyslipidaemia
• Hyper/hypothyroidism

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Healthy control
Ocular hypertension
Primary open angle glaucoma
Normal tension glaucoma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tissue bound AGE level (AU)	Level of AGE found in the skin - measured from the lower portion of the arm	Tissue bound AGE level (AU) will be measured for each participant at their second session (within 3 months of volunteering).

Collaborators and Investigators

• Sponsor: University of Plymouth

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Actual): July 1, 2018
• Study Completion (Actual): September 1, 2018

Study Registration Dates

• First Submitted: August 8, 2016
• First Submitted That Met QC Criteria: August 10, 2016
• First Posted (Estimate): August 11, 2016

Study Record Updates

• Last Update Posted (Actual): April 16, 2019
• Last Update Submitted That Met QC Criteria: April 15, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Optic Nerve Diseases; Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Low Tension Glaucoma
• Other Study ID Numbers: 204642