March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Membrane Attack Complex Induces Apoptosis In Retinal Ganglion Cells In Chronic Ocular Hypertension Model
Author Affiliations & Notes
  • Purushottam Jha
    Ophthalmology, Jones Eye Institute - UAMS, Little Rock, Arkansas
  • Valeriy V. Lyzogubov
    Ophthalmology, Jones Eye Institute - UAMS, Little Rock, Arkansas
  • Puran S. Bora
    Ophthalmology, Jones Eye Institute - UAMS, Little Rock, Arkansas
  • Nalini S. Bora
    Ophthalmology, Jones Eye Institute - UAMS, Little Rock, Arkansas
  • Footnotes
    Commercial Relationships  Purushottam Jha, None; Valeriy V. Lyzogubov, None; Puran S. Bora, None; Nalini S. Bora, None
  • Footnotes
    Support  Pat & Willard Walker Eye Research Center, Jones Eye Institute, Little Rock, AR.
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 6597. doi:
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      Purushottam Jha, Valeriy V. Lyzogubov, Puran S. Bora, Nalini S. Bora; Membrane Attack Complex Induces Apoptosis In Retinal Ganglion Cells In Chronic Ocular Hypertension Model. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6597.

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Abstract

Purpose: : To investigate the role of membrane attack complex (MAC)- the final product of complement activation, in the induction of apoptosis of retinal ganglionic cells in chronic ocular hypertension model.

Methods: : Intraocular pressure (IOP) was elevated in left eye of Lewis rats by laser photocoagulation (two treatments, 7 days apart) of episcleral and limbal veins. The right eye was left untreated and served as control. Lewis rats were injected with cobra venom factor (CVF, >30 units/rat, i.p.) at day 7, 14, 21, 28, 35 and 49 post-laser, to inhibit the MAC formation by depleting the complement system. These animals were sacrificed on day 49 post-laser. The control animals received similar treatment with equal volume of PBS. The retina was harvested from laser-treated eyes as well as untreated control eyes and processed for flatmounts and paraffin embedding. Flatmounts were used to stain for intracellular Ca2+ and MAC. Paraffin sections were used for immunostaining for glial fibrillary acidic protein (GFAP), MAC, caspase-3 and proteins involved in Ca2+ mediated signaling such as calcineurin, calpain, and cytochrome c.

Results: : Immunofluorescent staining demonstrated that the inhibition of MAC formation resulted in decreased GFAP staining in the retina of animals with elevated IOP. Reduced active caspase-3 staining in ganglionic cell layer was observed in the absence of MAC. Inhibition of MAC formation also resulted in reduced calcium influx and decreased level of proteins involved in Ca2+ mediated signaling pathways compared to PBS treated rats with increased IOP.

Conclusions: : Increased MAC deposition causes excess Ca2+ entry, which leads to apoptosis of RGCs in glaucoma. Thus, pharmacologic inhibition of MAC formation may have therapeutic benefits in the patients with glaucoma.

Keywords: apoptosis/cell death • calcium • ganglion cells 
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