| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 From the Kellogg Eye Center, University of Michigan, Ann Arbor; and 2 The Center for Ophthalmic Research, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts.
PURPOSE. To investigate possible protective effects of lens epithelium-derived growth factor (LEDGF) against photoreceptor death in light-damaged, Royal College of Surgeons (RCS) and P23H rhodopsin transgenic rats.
METHODS. Twelve-week-old Sprague–Dawley (SD), 6-week-old RCS, and 10-day-old P23H (line 1, heterozygote) rats received an intravitreal injection of LEDGF fused with glutathione-S-transferase (GST-LEDGF). Fellow eyes received vehicle and served as control specimens. Two days after the injections, the SD rats were exposed to light of 2000 lux for 48 hours. Corneal Ganzfeld ERGs were recorded 10 days after light damage, at 10 weeks of age in RCS rats, and at 4 weeks of age in P23H rats. The eyes were then processed for histologic analysis. Heat shock protein (hsp) content in the sensory retina was analyzed quantitatively by protein immunoblot.
RESULTS. In light-damaged rats, the ERG indicated retinal protection in
GST-LEDGF–injected eyes, with b-wave and STR thresholds being
1.14 ± 0.50 (mean ± SD) and 0.60 ± 0.26 log candela
(cd)/m2 lower, respectively, than in vehicle-injected eyes
(P < 0.01). The GST-LEDGF–treated eyes had
maximum b-wave amplitudes that were significantly larger
(P < 0.0005), had more than twice as many
remaining photoreceptors, and had better organized outer segments than
the control eyes. In RCS rats, the treated eyes had 2.76 ± 0.73
and 0.83 ± 0.09 log cd/m2 lower thresholds for the
b-wave and STR, respectively (P < 0.005), and had
significantly larger maximum b-wave amplitude (P <
0.0005). GST-LEDGF–treated eyes of RCS rats also had more
photoreceptors remaining (P < 0.005) and a thinner
debris layer than control eyes. In P23H rats, GST-LEDGF treatment did
not protect either retinal function or structure. The retinas from
GST-LEDGF–treated eyes of SD and RCS rats had higher levels of hsp25
and 
B-crystallin than vehicle-injected eyes.
CONCLUSIONS. GST-LEDGF protects photoreceptor structure and function in both
light-damaged and RCS rats. The increased expression of hsp25 and
B-crystallin may play a role in this protection. The absence of
rescue in P23H raises the possibility that some forms of inherited
retinal degeneration may not be amenable to treatment by intraocular
injection of LEDGF.
This article has been cited by other articles:
|
|
 |
|
  T. J. McGill, G. T. Prusky, R. M. Douglas, D. Yasumura, M. T. Matthes, G. Nune, K. Donohue-Rolfe, H. Yang, D. Niculescu, W. W. Hauswirth, et al. Intraocular CNTF Reduces Vision in Normal Rats in a Dose-Dependent Manner Invest. Ophthalmol. Vis. Sci., December 1, 2007; 48(12): 5756 - 5766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Morimoto, T. Fujikado, J.-S. Choi, H. Kanda, T. Miyoshi, Y. Fukuda, and Y. Tano Transcorneal Electrical Stimulation Promotes the Survival of Photoreceptors and Preserves Retinal Function in Royal College of Surgeons Rats Invest. Ophthalmol. Vis. Sci., October 1, 2007; 48(10): 4725 - 4732. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sakai, N. Kuno, F. Takamatsu, E. Kimura, H. Kohno, K. Okano, and K. Kitahara Prolonged Protective Effect of Basic Fibroblast Growth Factor-Impregnated Nanoparticles in Royal College of Surgeons Rats Invest. Ophthalmol. Vis. Sci., July 1, 2007; 48(7): 3381 - 3387. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. B. Wilson, K. Kunchithapautham, and B. Rohrer Paradoxical Role of BDNF: BDNF+/- Retinas Are Protected against Light Damage-Mediated Stress Invest. Ophthalmol. Vis. Sci., June 1, 2007; 48(6): 2877 - 2886. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Joly, V. Pernet, S. Chemtob, A. Di Polo, and P. Lachapelle Neuroprotection in the Juvenile Rat Model of Light-Induced Retinopathy: Evidence Suggesting a Role for FGF-2 and CNTF Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 2311 - 2320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Ishikawa, H. Ohguro, I. Ohguro, H. Yamazaki, K. Mamiya, T. Metoki, T. Ito, Y. Yokoi, and M. Nakazawa Prolonged Rhodopsin Phosphorylation in Light-Induced Retinal Degeneration in Rat Models Invest. Ophthalmol. Vis. Sci., December 1, 2006; 47(12): 5204 - 5211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Fatma, E. Kubo, L. T. Chylack Jr., T. Shinohara, Y. Akagi, and D. P. Singh LEDGF regulation of alcohol and aldehyde dehydrogenases in lens epithelial cells: stimulation of retinoic acid production and protection from ethanol toxicity Am J Physiol Cell Physiol, August 1, 2004; 287(2): C508 - C516. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Sharma, N. Fatma, E. Kubo, T. Shinohara, L. T. Chylack Jr., and D. P. Singh Lens Epithelium-derived Growth Factor Relieves Transforming Growth Factor-{beta}1-induced Transcription Repression of Heat Shock Proteins in Human Lens Epithelial Cells J. Biol. Chem., May 23, 2003; 278(22): 20037 - 20046. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Vollrath, W. Feng, J. L. Duncan, D. Yasumura, P. M. D'Cruz, A. Chappelow, M. T. Matthes, M. A. Kay, and M. M. LaVail Correction of the retinal dystrophy phenotype of the RCS rat by viral gene transfer of Mertk PNAS, October 23, 2001; 98(22): 12584 - 12589. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
