title: Retina Is Protected by Neuroserpin from Ischemic/Reperfusion-Induced Injury Independent of Tissue-Type Plasminogen Activator.
abstract: The purpose of the present study was to investigate the potential neuroprotective effect of neuroserpin (NSP) on acute retinal ischemic/reperfusion-induced (IR) injury. An IR injury model was established by elevating intraocular pressure (IOP) for 60 minutes in wild type and tPA-deficient (tPA-/-) mice. Prior to IR injury, 1 μL of 20 μmol/L NSP or an equal volume of bovine serum albumin (BSA) was intravitreally administered. Retinal function was evaluated by electroretinograph (ERG) and the number of apoptotic neurons was determined via TUNEL labeling. Caspase-3, -8, -9,poly (ADP-ribose) polymerase (PARP)and their cleaved forms were subsequently analyzed. It was found that IR injury significantly damaged retinal function, inducing apoptosis in the retina, while NSP attenuated the loss of retinal function and significantly reduced the number of apoptotic neurons in both wild type and tPA-/- mice. The levels of cleaved caspase-3, cleaved PARP (the substrate of caspase-3) and caspase-9 (the modulator of the caspase-3), which had increased following IR injury, were significantly inhibited by NSP in both wild type and tPA-/- mice. NSP increased ischemic tolerance in the retina at least partially by inhibiting the intrinsic cell death signaling pathway of caspase-3. It was therefore concluded that the protective effect of neuroserpin maybe independent from its canonical interaction with a tissue-type plasminogen activator.
authors.affiliation: Department of Ophthalmology and Vision Sciences and Key Laboratory of Myopia of State Health Ministry, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, China.
authors.forename: R P
authors.initials: RP
authors.lastname: Gu
authors.affiliation: Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: L L
authors.initials: LL
authors.lastname: Fu
authors.affiliation: Department of Ophthalmology and Vision Sciences and Key Laboratory of Myopia of State Health Ministry, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, China; Department of Ophthalmology, No. 5 people's Hospital of Shanghai, Shanghai, 200240, China.
authors.forename: C H
authors.initials: CH
authors.lastname: Jiang
authors.affiliation: Department of Ophthalmology and Vision Sciences and Key Laboratory of Myopia of State Health Ministry, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, China.
authors.forename: Y F
authors.initials: YF
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology and Vision Sciences and Key Laboratory of Myopia of State Health Ministry, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology and Vision Sciences and Key Laboratory of Myopia of State Health Ministry, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, China.
authors.forename: J
authors.initials: J
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053453:Caspase 9 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009479:Neuropeptides / Q000378:metabolism* / Q000494:pharmacology; D000066829:Neuroprotection; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D012160:Retina / Q000166:cytology / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D015843:Serpins / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D010959:Tissue Plasminogen Activator / Q000172:deficiency / Q000378:metabolism*; D000097522:Neuroserpin
chemical_list: D053453:Caspase 9; D009479:Neuropeptides; D015843:Serpins; D010959:Tissue Plasminogen Activator; D000097522:Neuroserpin