Morphometric analysis of lipoprotein-like particle accumulation in aging human macular Bruch's membrane

Jiahn-Dar Huang1, Christine A Curcio, Mark Johnson

  • 1Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208-3107, USA.

Abstract

Insights

Lipoprotein-like particles (LLPs) accumulate with age in Bruch's membrane (BrM), primarily in the inner and elastic layers. This accumulation, linked to retinal pigment epithelium (RPE) cells, contributes significantly to age-related lipid buildup in BrM.

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Biochemistry

Background:

  • Bruch's membrane (BrM) is a crucial layer in the retina.
  • Age-related changes in BrM contribute to vision impairment.
  • Lipoprotein-like particles (LLPs) are implicated in BrM pathology.

Purpose of the Study:

  • To quantify the size and distribution of age-accumulated lipoprotein-like particles (LLPs) within Bruch's membrane (BrM).
  • To investigate the regional differences in LLP accumulation in BrM.
  • To correlate LLP accumulation with age-related changes in BrM.

Main Methods:

  • Human BrM specimens (ages 27-78) were prepared using quick-freeze/deep-etch electron microscopy.
  • Stereologic analysis was employed to quantify LLP volume fraction and diameter.
  • Regional analysis was performed across different BrM layers (ICL, EL, OCL).

Main Results:

  • LLP volume fraction increased with age in the inner collagenous layer (ICL) and elastic layer (EL), but not the outer collagenous layer (OCL).
  • Total LLP-associated lipid mass in BrM increased with age.
  • LLP size did not significantly increase with age, but showed modest growth with higher LLP volume.

Conclusions:

  • The accumulation pattern suggests a retinal pigment epithelium (RPE) origin for LLPs.
  • LLPs fill the EL and ICL before accumulating near the RPE, explaining the lack of OCL accumulation.
  • LLP-associated lipids constitute a major component of age-related lipid accumulation in BrM.

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