May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
PERG Analysis Detects Physiological Dysfunction Prior to Ganglion Cell Loss in the DBA/2J Mouse Glaucoma Model
Author Affiliations & Notes
  • R.T. Libby
    Jackson Laboratory, Bar Harbor, ME
  • V. Porciatti
    Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL
  • M. Tapia
    Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL
  • R.K. Lee
    Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL
  • S.W. M. John
    Jackson Laboratory, Bar Harbor, ME
    Howard Hughes Medical Institute, Bar Harbor, ME
  • Footnotes
    Commercial Relationships  R.T. Libby, None; V. Porciatti, None; M. Tapia, None; R.K. Lee, None; S.W.M. John, None.
  • Footnotes
    Support  VP, EY016322 HIGHWIRE EXLINK_ID="47:5:4005:1" VALUE="EY016322" TYPEGUESS="GEN" /HIGHWIRE ; RKL EY016775 HIGHWIRE EXLINK_ID="47:5:4005:2" VALUE="EY016775" TYPEGUESS="GEN" /HIGHWIRE ; SWMJ is an Investigator of the Howard Hughes Medical Institute
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 4005. doi:
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      R.T. Libby, V. Porciatti, M. Tapia, R.K. Lee, S.W. M. John; PERG Analysis Detects Physiological Dysfunction Prior to Ganglion Cell Loss in the DBA/2J Mouse Glaucoma Model . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4005.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : DBA/2J (D2) mice develop a pigment–liberating iris disease around 5 months of age due to mutations in two genes. This iris disease typically results in elevated intraocular pressure (IOP) around 8 months and severe glaucoma by one year. The pattern electroretinogram (PERG) measures activity of inner retinal neurons, including retinal ganglion cells (RGCs). We tested if PERG amplitude correlates to RGC loss and/or if PERG can detect early RGC functional defects in D2 mice.

Methods: : PERGs were performed on D2 mice (n=30 eyes) aged 10 to 11 months, a period when glaucomatous damage to optic nerves is variable. After PERG, the optic nerves were removed and the severity of glaucomatous damage to each optic nerve was graded as mild, moderate or severe. PERG amplitudes for D2 mice were compared to control, age–matched D2 mice that were wild–type for one of the iris disease genes and do not have high IOP (D2–congenic, n=16). C57BL/6J (B6) mice congenic for both D2 iris disease genes (B6–congenic) were controls for the effect of iris disease on the PERG. B6–congenic mice develop severe iris disease but do not develop elevated IOP (n=40, before iris disease; n=31, severe iris disease).

Results: : No correlation was observed between PERG amplitude and optic nerve grade in 10–11 month–old D2 mice (R2=0.024). PERG amplitudes of nerves with mild damage were similar in amplitude to those with severe damage (mean µv ± SEM; mild, 2.68 ± 0.49 n=17; severe, 2.25 ± 0.36, n=15; P=0.47). However, PERG amplitudes of D2 mice with mild damage were reduced by 63% compared to aged matched, control D2 congenic mice (7.25 ± 0.98 n=20; P<0.001). Importantly, no significant difference (P=0.22) in PERG amplitudes was observed between young B6–congenic mice (normal iris) and aged B6–congenic mice (severe iris disease).

Conclusions: : The PERG amplitude of D2 mice at 10–11 months of age is markedly reduced compared to age–matched D2–congenic mice. In contrast, the PERG of old B6 mice with iris disease is normal, thereby excluding the possibility that PERG reduction in old D2 mice is due to non–neural factors caused by iris disease. In old D2 mice, the PERG amplitude did not correlate to glaucomatous optic nerve damage, probably because early functional damage already reduced PERG amplitude significantly, leaving little room for further amplitude decreases. Altogether, our results suggest that elevated IOP has an important effect on inner retinal activity prior to detectable morphological damage.

Keywords: ganglion cells • genetics • degenerations/dystrophies 
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