Retinal and choroidal microangiopathies: Therapeutic opportunities

A. Afzal, L. C. Shaw, A. V. Ljubimov, M. E. Boulton, M. S. Segal, M. B. Grant

Research output: Contribution to journalReview articlepeer-review

57 Scopus citations

Abstract

Pathological angiogenesis in the retina and underlying choroid is a major cause of visual impairment in all age groups. The last decade has seen an explosion in the clinical availability of antiangiogenic compounds. Emphasis has been placed on inhibitors of the VEGF signaling pathway and considerable success has been achieved with aptamers and antibodies that bind VEGF. However, regression of neovascularization is rarely permanent and the regrowth of new vessels, often within a few months, requires multiple applications of drug. A number of antiangiogenic factors such as IGFBP3, SDF-1 blockers, PEDF, γ-secretase, Delta-like ligand 4, and integrin antagonists have been identified, which act either indirectly on the VEGF system or independent of it. The importance of other candidates such as HIF-1α and protein kinase CK2, which act as "master" regulators of angiogenesis, offer realistic alternative targets for pharmacological intervention. The concept of combination therapy is rapidly gaining interest in the eye field and co-administration of two angiogenic agents (e.g., a CK2 inhibitor with a somatostatin analog, octreotide) are often significantly more effective at inhibiting retinal angiogenesis than either drug alone. The following review will discuss the current therapies available for aberrant ocular angiogenesis, consider new candidate targets for development of antiangiogenic compounds and emphasize the importance of combinatorial pharmacological agents in the treatment of such a dynamic cellular event as angiogenesis.

Original languageEnglish (US)
Pages (from-to)131-144
Number of pages14
JournalMicrovascular Research
Volume74
Issue number2-3
DOIs
StatePublished - Sep 1 2007

Keywords

  • Age-related macular degeneration
  • Angiogenesis
  • Antiangiogenic
  • CD133
  • CD14
  • CD34
  • CXCR4
  • Choroidal neovascularization
  • Delta-like ligand 4
  • Endothelial progenitor cell
  • Hematopoietic stem cell
  • Hypoxia
  • IGF-1
  • IGF-1R
  • IGFBP-3
  • Ischemia
  • PEDF
  • Proliferative retinopathy
  • Protein kinase CK2
  • Retinopathy of prematurity
  • SDF-1
  • Somatostatin analogs
  • Therapies
  • VEGF
  • VEGFR-1
  • VEGFR-2
  • Vascularization
  • γ-secretase

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

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