Aplicación de modelos genéticamente manipulados "knoch-out" en neuro-oftalmología.

Résumé

Our purpose was to study the functions of the ApoE, PTEN and P27kip1 proteins, in the optic nerve (ON) and retina. This study has been carried out with mice distributed in five groups: 1) wildtype mice (Control group), 2)ApoE Knockout mice (ApoE group), 3) ApoE Knockout mice fed with high cholesterol diet (ApoE+ D group), 4) PTEN heterocigotus Knockout mice, (PTEN group) and 5) P27kip1 Knockout mice (P27 group). In the ApoE and ApoE+ D groups, the cross-sectional areas of the ON and axons were significantly higher than in the Control group (P< 0.001, P< 0.001). Morphological alterations were detected in the macroglial cells, axons and myelin sheaths. No significant changes were noticed in the ON between the ApoE and the ApoE+ D mice. ApoE and ApoE+ D groups showed a significant reduction in the retinal thickness (P< 0.001, P< 0.001), which was more important in the group fed with hypercholeterolemic diet. In the P27 group, the ON cross-sectional area was significantly higher than in the Control group (P< 0.001). This increase was accompanied with an increment in the total number of optic fibres. Ultraestructural alterations were detected in astrocytes, oligodendrocytes, axons and myelin. The P27 group also showed a significant decrease in the retinal thickness with important morphological alterations. In PTEN group, the ON and the axonal transversal areas were significantly higher than in the Control group (P< 0.001). We can conclude that the no-expression of ApoE induces in the ON mice an hypertrophic pattern with important structural alterations, independently with the lipidic cholesterol levels. An hypotrophic pattern was present in the retinas of these animals. The absence in the expression of P27kip1 protein induces hypertrophia and hyperplasia in the ON, while signs of disorganization and atrophy are presents in the retina. Lastly, the no-expression of PTEN protein induces, in the ON and retina, a hypertrophic pattern.