Lens epithelium-derived growth factor promotes photoreceptor survival in light-damaged and RCS rats

S. Machida, P. Chaudhry, T. Shinohara, D. P. Singh, V. N. Reddy, Jr Chylack, P. A. Sieving, R. A. Bush

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

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 αB-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 αB-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.

Original languageEnglish (US)
Pages (from-to)1087-1095
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume42
Issue number5
StatePublished - Apr 23 2001

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Light
Crystallins
Retina
lens epithelium-derived growth factor
Surgeons
Intraocular Injections
Transgenic Rats
Retinal Degeneration
Intravitreal Injections
Rhodopsin
Intraocular Lenses
Heterozygote
Heat-Shock Proteins
Glutathione Transferase
Sprague Dawley Rats
Injections
Therapeutics
Proteins

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Machida, S., Chaudhry, P., Shinohara, T., Singh, D. P., Reddy, V. N., Chylack, J., ... Bush, R. A. (2001). Lens epithelium-derived growth factor promotes photoreceptor survival in light-damaged and RCS rats. Investigative Ophthalmology and Visual Science, 42(5), 1087-1095.

Lens epithelium-derived growth factor promotes photoreceptor survival in light-damaged and RCS rats. / Machida, S.; Chaudhry, P.; Shinohara, T.; Singh, D. P.; Reddy, V. N.; Chylack, Jr; Sieving, P. A.; Bush, R. A.

In: Investigative Ophthalmology and Visual Science, Vol. 42, No. 5, 23.04.2001, p. 1087-1095.

Research output: Contribution to journalArticle

Machida, S, Chaudhry, P, Shinohara, T, Singh, DP, Reddy, VN, Chylack, J, Sieving, PA & Bush, RA 2001, 'Lens epithelium-derived growth factor promotes photoreceptor survival in light-damaged and RCS rats', Investigative Ophthalmology and Visual Science, vol. 42, no. 5, pp. 1087-1095.
Machida, S. ; Chaudhry, P. ; Shinohara, T. ; Singh, D. P. ; Reddy, V. N. ; Chylack, Jr ; Sieving, P. A. ; Bush, R. A. / Lens epithelium-derived growth factor promotes photoreceptor survival in light-damaged and RCS rats. In: Investigative Ophthalmology and Visual Science. 2001 ; Vol. 42, No. 5. pp. 1087-1095.
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T1 - Lens epithelium-derived growth factor promotes photoreceptor survival in light-damaged and RCS rats

AU - Machida, S.

AU - Chaudhry, P.

AU - Shinohara, T.

AU - Singh, D. P.

AU - Reddy, V. N.

AU - Chylack, Jr

AU - Sieving, P. A.

AU - Bush, R. A.

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N2 - 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 αB-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 αB-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.

AB - 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 αB-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 αB-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.

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