Nanosecond laser therapy reverses pathologic and molecular changes in age-related macular degeneration without retinal damage

FASEB J. 2015 Feb;29(2):696-710. doi: 10.1096/fj.14-262444. Epub 2014 Nov 12.

Abstract

Age-related macular degeneration (AMD) is a leading cause of vision loss, characterized by drusen deposits and thickened Bruch's membrane (BM). This study details the capacity of nanosecond laser treatment to reduce drusen and thin BM while maintaining retinal structure. Fifty patients with AMD had a single nanosecond laser treatment session and after 2 yr, change in drusen area was compared with an untreated cohort of patients. The retinal effect of the laser was determined in human and mouse eyes using immunohistochemistry and compared with untreated eyes. In a mouse with thickened BM (ApoEnull), the effect of laser treatment was quantified using electron microscopy and quantitative PCR. In patients with AMD, nanosecond laser treatment reduced drusen load at 2 yr. Retinal structure was not compromised in human and mouse retina after laser treatment, with only a discrete retinal pigment epithelium (RPE) injury, and limited mononuclear cell response observed. BM was thinned in the ApoEnull mouse 3 mo after treatment (ApoEnull treated 683 ± 38 nm, ApoEnull untreated 890 ± 60 nm, C57Bl6J 606 ± 43 nm), with the expression of matrix metalloproteinase-2 and -3 increased (>260%). Nanosecond laser resolved drusen independent of retinal damage and improved BM structure, suggesting this treatment has the potential to reduce AMD progression.

Keywords: Bruch’s membrane; drusen; matrix metalloproteinase; vision loss.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging
  • Animals
  • Bruch Membrane / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Laser Therapy*
  • Macular Degeneration / physiopathology
  • Macular Degeneration / therapy*
  • Male
  • Matrix Metalloproteinases / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Pilot Projects
  • Polymerase Chain Reaction
  • Prospective Studies
  • Retina / physiopathology*
  • Retinal Diseases / physiopathology
  • Retinal Diseases / therapy*
  • Retinal Pigment Epithelium / pathology

Substances

  • Matrix Metalloproteinases