Changes in murine hyalocytes are valuable early indicators of ocular disease.
OBJECTIVE
The distribution, density, and phenotype of hyalocytes or vitreous macrophages in mouse eyes was examined during normal aging and in models of background diabetic retinopathy, retinal vascular proliferation, and exposure to TLR4 and TLR9 ligands.


METHODS
The phenotype and density of hyalocytes were investigated in retinal and ciliary body wholemounts of normal wild-type (WT; C57BL/6) mice at 7, 17, and 120 weeks of age, Ins2(Akita) mice, transgenic Kimba mice (VEGF-induced retinal neovascularization), and WT mice 24 hours after single intraperitoneal injection with lipopolysaccharide (LPS) or 1 week after three identical doses administered 2 weeks apart. Another group of mice each received a single topical drop of 20 μg CpG-oligodeoxynucleotides (CpG-ODN) to the abraded corneal surface and were euthanized 1 week later.


RESULTS
The data revealed an approximately fivefold increase in the density of preretinal hyalocytes in 120-week-old mice. Some hyalocytes in older eyes contained phagocytosed melanin. Hyalocyte density was doubled in Ins2(Akita) mice after only 3 to 4 weeks of hyperglycemia. Kimba mice had an eightfold increase in the density of hyalocytes, and many displayed signs of activation. WT mice exposed to single or multiple systemic doses of LPS showed a twofold to threefold increase in hyalocytes. Topical CpG-ODN treatment led to a very marked (sevenfold) increase in preretinal hyalocyte density.


CONCLUSIONS
The present study demonstrated that murine hyalocytes were responsive to aging, hyperglycemia, locally produced VEGF, and both systemic and ocular-derived TLR ligands. Thus hyalocytes or vitreous macrophages may be a valuable and previously unrecognized sensitive indicator of pathologic changes in the eye.
Department of Molecular Ophthalmology, Centre for Ophthalmology and Visual Science, University of Western Australia, Crawley, Australia.
Nina N
NN
Vagaja
Holly R
HR
Chinnery
Nicolette
N
Binz
Jelena M
JM
Kezic
Elizabeth P
EP
Rakoczy
Paul G
PG
McMenamin
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000375:Aging / Q000502:physiology; D000818:Animals; D003930:Diabetic Retinopathy / Q000473:pathology*; D004195:Disease Models, Animal; D007328:Insulin / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D015861:Retinal Neovascularization / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D014822:Vitreous Body / Q000473:pathology* / Q000502:physiology
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; C561967:Ins2 protein, mouse; D007328:Insulin; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; D042461:Vascular Endothelial Growth Factor A