Neurotrophic factors minimize the retinal toxicity of verteporfin photodynamic therapy.
OBJECTIVE
A prior study showed that brain-derived neurotrophic factor (BDNF) rescues photoreceptors from collateral retinal damage caused by photodynamic therapy (PDT). This study was conducted to determine whether ciliary neurotrophic factor (CNTF), a combination of BDNF and CNTF, or pigment epithelial cell-derived growth factor (PEDF) might protect photoreceptors and retinal function more effectively than BDNF. Also investigated was whether protection would be observed after a second round of PDT with adjunctive BDNF treatment.


METHODS
Normal rats received intravitreal injections of BDNF, CNTF, a combination of BDNF and CNTF, or PEDF in one eye and PBS in the other 2 days before PDT. Retinal function and photoreceptor survival were assessed with multifocal ERG (mfERG) and histology 1 week after PDT. Another group of rats received two courses of PDT 3 months apart, with injection of BDNF 2 days before each treatment.


RESULTS
All factors significantly increased photoreceptor survival. The combination of BDNF and CNTF rescued more photoreceptors than either factor alone. Only BDNF improved retinal function 1 week after PDT, with CNTF and the combination of BDNF and CNTF reducing mfERG responses. BDNF injection before a second round of PDT improved mfERG responses and retinal structure.


CONCLUSIONS
BDNF is the most effective single factor among those tested for neuroprotection and improvement of retinal function after PDT, although a combination of BDNF and CNTF rescues more photoreceptors. Adjunctive treatment with BDNF also protects retinal structure and function through two rounds of PDT, suggesting its potential value for patients who require multiple treatments.
Paskowitz
Daniel M
DM
Department of Ophthalmology, University of California, San Francisco, California 94143, USA.
Donohue-Rolfe
Kate M
KM
Yang
Haidong
H
Yasumura
Douglas
D
Matthes
Michael T
MT
Hosseini
Kamran
K
Graybeal
Carolyn M
CM
Nune
George
G
Zarbin
Marco A
MA
Lavail
Matthew M
MM
Duncan
Jacque L
JL
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D020934:Ciliary Neurotrophic Factor / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004596:Electroretinography / Q000187:drug effects; D005136:Eye Proteins / Q000627:therapeutic use; D007267:Injections; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010778:Photochemotherapy; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000473:pathology; D017319:Photosensitizing Agents / Q000633:toxicity*; D011166:Porphyrins / Q000633:toxicity*; D051381:Rats; D011914:Rats, Inbred BN; D012160:Retina / Q000187:drug effects / Q000502:physiology; D012164:Retinal Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D015843:Serpins / Q000627:therapeutic use; D000077362:Verteporfin; D014822:Vitreous Body; D000099174:Pigment Epithelium-Derived Factor
D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; D005136:Eye Proteins; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D017319:Photosensitizing Agents; D011166:Porphyrins; D015843:Serpins; D000077362:Verteporfin; D000099174:Pigment Epithelium-Derived Factor