Retinal neurodegeneration in the DBA/2J mouse-a model for ocular hypertension.
Mice of the DBA/2J strain spontaneously develop complex ocular abnormalities, including glaucomatous loss of retinal ganglion cells (RGC). In the present study ultrastructural features of retinal neurodegeneration in DBA/2J mice of different age (3, 6, 8 and 11 months) are described. By 3 months, RGC apoptosis characterized by electron-dense karioplasm and cytoplasm of ganglion cells was observed. The occurrence of apoptotic ganglion cells peaked at the age of 6 months. Past this age, necrosis characterized by swelling and electron-rare cytoplasm appeared to be the prevailing form of cell death. Müller glia activation increased with age, but there were no signs of leukocyte infiltration. At 8 and 11 months, signs of neoangiogenesis were found both at the ultrastructural level and in clinical examinations. In these older animals myelin-like bodies, most probably representing the intracellular aggregates of phospholipids in irreversibly injured cells, were also seen. Photoreceptor cells were not affected at any age. Our observations suggest that retinal degeneration in the DBA/2J mice does not involve recruitment of blood-borne inflammatory/phagocytosing cells, and that apoptosis is gradually replaced by necrosis as the predominant pathway of RGC death. Retinal degeneration in 3- to 11-month-old DBA/2J mice partially resembles human pigment dispersion syndrome and pigmentary glaucoma with characteristic anterior segment changes and elevation of intraocular pressure. However, neovasculogenesis and myelin-like bodies are observed during aging. Therefore, the DBA/2J model requires judicious interpretation as a glaucoma model.
Schuettauf
Frank
F
Experimental Ophthalmology, University Eye Hospital, Roentgenweg 11, 72076, Tuebingen, Germany. fschuettauf@uni-tuebingen.de
Rejdak
Robert
R
Walski
Michal
M
Frontczak-Baniewicz
Malgorzata
M
Voelker
Michael
M
Blatsios
Georgios
G
Shinoda
Kei
K
Zagorski
Zbigniew
Z
Zrenner
Eberhart
E
Grieb
Pawel
P
D000367:Age Factors; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron / Q000379:methods; D009457:Neuroglia / Q000473:pathology / Q000648:ultrastructure; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure; D009798:Ocular Hypertension / Q000150:complications* / Q000473:pathology*; D012160:Retina / Q000473:pathology / Q000648:ultrastructure; D012162:Retinal Degeneration / Q000209:etiology* / Q000473:pathology*