PMID- 27158920
OWN - NLM
STAT- MEDLINE
DCOM- 20171018
LR  - 20181113
IS  - 1460-2202 (Electronic)
IS  - 0271-3683 (Print)
IS  - 0271-3683 (Linking)
VI  - 41
IP  - 11
DP  - 2016 Nov
TI  - An Experimental Animal Model of Photodynamic Optic Nerve Head Injury (PONHI).
PG  - 1498-1506
AB  - PURPOSE: Anterior ischemic optic neuropathy (AION) is the most common cause of 
      non-glaucomatous optic nerve head (ONH) injury among older adults. AION results 
      from a sudden ischemic insult to the proximal portion of the optic nerve, 
      typically leading to visual impairment. Here, we present an experimental model of 
      photodynamically induced ONH injury that can be used to study neuroprotective 
      modalities. METHODS: Intraperitoneal injection of mesoporphyrin IX was followed 
      by photodynamic treatment of the ONH in one eye of Brown-Norway rats; the fellow 
      eye received the reverse sequence as a sham control. Fluorescein angiography 
      (FA), spectral domain optical coherence tomography (SD-OCT), and visual evoked 
      potential (VEP) recordings were performed at different time points following 
      laser treatment. Immunohistochemistry was used to monitor apoptotic cell death 
      (TUNEL) and macrophage infiltration (CD68). Cytokine levels were evaluated using 
      enzyme-linked immunosorbent assay (ELISA). RESULTS: FA showed early 
      hyperfluorescence and late leakage of the ONH, while SD-OCT revealed optic nerve 
      edema. No leakage or other abnormalities were detected in control eyes. VEPs were 
      significantly reduced in amplitude and showed prolonged responses compared to 
      sham eyes. The number of apoptotic retinal ganglion cells was elevated one day 
      after laser treatment (13.77 +/- 4.49, p < 0.01) and peaked on day 7 (57.22 +/- 
      11.34, p < 0.01). ONH macrophage infiltration also peaked on day 7 (101.8 +/- 9.8, 
      p < 0.05). ELISAs performed showed upregulation of macrophage chemoattractant 
      protein-1 and macrophage inflammatory protein-2 on days 3 and 1, respectively. 
      CONCLUSIONS: Photodynamic treatment of the ONH after administration of 
      mesoporphyrin IX leads to macroscopic, histologic, and physiologic evidence of 
      ONH injury. Given the long half-life of mesoporphyrin IX and the ease of 
      intraperitoneal injections, this new model of photodynamically induced ONH injury 
      may be a useful tool for studying optic nerve injury and possible neuroprotective 
      treatments.
FAU - Mantopoulos, Dimosthenis
AU  - Mantopoulos D
AD  - a Neuro-Ophthalmology Service, Department of Ophthalmology, Massachusetts Eye and 
      Ear Infirmary , Harvard Medical School , Boston , MA , USA.
AD  - b Retina Service, Department of Ophthalmology , Massachusetts Eye and Ear 
      Infirmary, Harvard Medical School , Boston , MA , USA.
FAU - Bouzika, Peggy
AU  - Bouzika P
AD  - a Neuro-Ophthalmology Service, Department of Ophthalmology, Massachusetts Eye and 
      Ear Infirmary , Harvard Medical School , Boston , MA , USA.
AD  - b Retina Service, Department of Ophthalmology , Massachusetts Eye and Ear 
      Infirmary, Harvard Medical School , Boston , MA , USA.
FAU - Tsakris, Athanassios
AU  - Tsakris A
AD  - d Department of Microbiology , Medical School, University of Athens , Athens , 
      Greece.
FAU - Pawlyk, Basil S
AU  - Pawlyk BS
AD  - c Berman-Gund Laboratory for the Study of Retinal Degenerations, Department of 
      Ophthalmology , Massachusetts Eye and Ear Infirmary, Harvard Medical School , 
      Boston , MA , USA.
FAU - Sandberg, Michael A
AU  - Sandberg MA
AD  - c Berman-Gund Laboratory for the Study of Retinal Degenerations, Department of 
      Ophthalmology , Massachusetts Eye and Ear Infirmary, Harvard Medical School , 
      Boston , MA , USA.
FAU - Miller, Joan W
AU  - Miller JW
AD  - b Retina Service, Department of Ophthalmology , Massachusetts Eye and Ear 
      Infirmary, Harvard Medical School , Boston , MA , USA.
FAU - Rizzo Iii, Joseph F
AU  - Rizzo Iii JF
AD  - a Neuro-Ophthalmology Service, Department of Ophthalmology, Massachusetts Eye and 
      Ear Infirmary , Harvard Medical School , Boston , MA , USA.
FAU - Vavvas, Demetrios G
AU  - Vavvas DG
AD  - b Retina Service, Department of Ophthalmology , Massachusetts Eye and Ear 
      Infirmary, Harvard Medical School , Boston , MA , USA.
FAU - Cestari, Dean M
AU  - Cestari DM
AD  - a Neuro-Ophthalmology Service, Department of Ophthalmology, Massachusetts Eye and 
      Ear Infirmary , Harvard Medical School , Boston , MA , USA.
LA  - eng
GR  - R01 EY025362/EY/NEI NIH HHS/United States
PT  - Journal Article
DEP - 20160509
PL  - England
TA  - Curr Eye Res
JT  - Current eye research
JID - 8104312
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Disease Models, Animal
MH  - Evoked Potentials, Visual
MH  - Fluorescein Angiography
MH  - Fundus Oculi
MH  - Male
MH  - Optic Disk/*pathology
MH  - Optic Neuropathy, Ischemic/etiology/*pathology/physiopathology
MH  - Photochemotherapy/*adverse effects
MH  - Rats
MH  - Rats, Inbred BN
MH  - Retinal Ganglion Cells/*pathology
MH  - Tomography, Optical Coherence/methods
PMC - PMC5412985
MID - NIHMS856315
OTO - NOTNLM
OT  - Animal model
OT  - mesoporphyrin IX
OT  - neuroprotection
OT  - optic nerve head injury
OT  - photodynamic treatment
COIS- Declaration of interest The authors report no conflicts of interest
EDAT- 2016/05/10 06:00
MHDA- 2017/10/19 06:00
PMCR- 2017/05/02
CRDT- 2016/05/10 06:00
PHST- 2016/05/10 06:00 [pubmed]
PHST- 2017/10/19 06:00 [medline]
PHST- 2016/05/10 06:00 [entrez]
PHST- 2017/05/02 00:00 [pmc-release]
AID - 10.3109/02713683.2015.1135960 [doi]
PST - ppublish
SO  - Curr Eye Res. 2016 Nov;41(11):1498-1506. doi: 10.3109/02713683.2015.1135960. Epub 
      2016 May 9.