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Updated: Jun 2, 2026
Enrichment of Bruch's Membrane from Human Donor Eyes
Published on: November 15, 2015
Disturbed matrix metalloproteinase activity of Bruch's membrane in age-related macular degeneration
Ali A Hussain1, Yunhee Lee, Jin-Jun Zhang
1Division of Molecular Therapy, UCL Institute of Ophthalmology, University of London, London, United Kingdom.
Purpose:
To evaluate the potential role of the matrix metalloproteinase (MMP) system of Bruch's membrane in the pathology of age-related macular degeneration.
Methods:
Free and bound pools of gelatinase activity in Bruch's membrane-choroid preparations were isolated by phosphate-buffered saline (PBS) and sodium dodecyl sulfate (SDS) extraction, respectively. Individual MMP species were separated by gelatin-substrate zymography and the levels were quantified by densitometric techniques. Altogether, 13 control (age range, 71-99 years) and 6 AMD (age range, 71-95 years) donor eyes were used.
Results:
All the gelatinase components normally present in control samples were also present in AMD tissue without any significant differences in their molecular masses. Total levels (bound plus free) of active MMP2 and -9 were significantly reduced in AMD donors (P < 0.05). The decrease in active MMP2 may be attributable to a similar reduction in the level of free pro-MMP2, the precursor to the active form. Reduction in active MMP9 occurred despite a nearly 3.5-fold increase in free pro-MMP9. The high-molecular-mass gelatinases denoted by HMW1 and -2 and comprising homo- and heteropolymers of pro-MMP2 and -9 were also raised in AMD (P < 0.05). The sequestration of free pro-MMP2 and -9 by these high-molecular-mass complexes may further contribute to reduced rates of activation of MMPs.
Conclusions:
The reduction in the levels of activated MMP2 and -9 may be responsible for impaired matrix degradation of Bruch's membrane, leading to the pathology associated with AMD. The degradation pathway is therefore a viable therapeutic target for future intervention.
Insights
Reduced active matrix metalloproteinases (MMPs) in Bruch's membrane may drive age-related macular degeneration (AMD) pathology. Targeting MMP degradation pathways offers a potential therapeutic strategy for AMD.
Area of Science:
- Ophthalmology
- Biochemistry
- Cell Biology
Background:
- Age-related macular degeneration (AMD) is a leading cause of vision loss.
- Bruch's membrane integrity is crucial for retinal health.
- The role of matrix metalloproteinases (MMPs) in AMD pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the matrix metalloproteinase (MMP) system within Bruch's membrane.
- To evaluate the MMP system's involvement in the pathology of age-related macular degeneration (AMD).
Main Methods:
- Gelatinase activity in Bruch's membrane-choroid preparations was assessed using phosphate-buffered saline (PBS) and sodium dodecyl sulfate (SDS) extraction.
- Matrix metalloproteinase (MMP) species were identified and quantified using gelatin-substrate zymography.
- Donor eyes from control subjects and AMD patients were analyzed.
Main Results:
- Active matrix metalloproteinases (MMPs) -2 and -9 levels were significantly reduced in AMD donors.
- A decrease in active MMP-2 correlated with reduced free pro-MMP-2.
- Elevated high-molecular-mass MMP complexes (HMW1, HMW2) were observed in AMD, potentially sequestering active MMPs.
Conclusions:
- Reduced levels of activated MMP-2 and MMP-9 may impair matrix degradation in Bruch's membrane, contributing to AMD.
- The MMP degradation pathway represents a potential therapeutic target for AMD intervention.
