| First Author | Sappington RM | Year | 2003 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 44 |
| Issue | 9 | Pages | 3725-31 |
| PubMed ID | 12939285 | Mgi Jnum | J:85228 |
| Mgi Id | MGI:2673114 | Doi | 10.1167/iovs.03-0039 |
| Citation | Sappington RM, et al. (2003) Optic nerve degeneration in a murine model of juvenile ceroid lipofuscinosis. Invest Ophthalmol Vis Sci 44(9):3725-31 |
| abstractText | PURPOSE: To investigate optic nerve degeneration associated with CLN3 deficiency in a murine model of juvenile neuronal ceroid lipofuscinosis (Batten disease). METHODS: Using light and electron microscopy, the density and diameter of axons and the thickness of myelin in optic nerve were compared between age-matched cln3 knock-out (cln3-/-) and wild-type (129ev/TAC) mice. Western blot analysis was used to assay expression of Cln3 in mouse and primate retina and optic nerve. RESULTS: Morphologically identified mast cells were present in the meningeal sheaths surrounding the cln3-/- nerve and in the nerve itself. The cln3-/- optic nerve exhibited an overall loss of uniformity and integrity. Axon density in cln3-/- optic nerve was only 64% of that in wild-type optic nerve (P < 0.01). Accounting for differences in axon density, the diameter of axons in cln3-/- optic nerve was 1.2 times greater than in wild-type optic nerve (P < 0.01). Electron micrographs revealed large spaces between axons and 32% thinner myelin surrounding axons in cln3-/- mice than in wild type (P < 0.01). Western blot analysis demonstrated that Cln3 was expressed in retinas and optic nerves of mouse and primate. CONCLUSIONS: The presence of apparent mast cells in cln3-/- optic nerve suggests compromise of the blood-brain barrier. The absence of Cln3 causes loss of axons, axonal hypertrophy, and a reduction in myelination of retinal ganglion cells. Furthermore, expression of CLN3 in mouse and primate optic nerve links degeneration to loss of Cln3. |
