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, 11 1.1.3) Organisation antéro-postérieure de l'oeil

.. .. La-rétine, 2.1.3) Organisation centre-périphérie : macula et fovéa

.. .. Histologie-de-la-rétine,

L. and .. .. ,

.. .. Le-réseau-vasculaire-rétinien,

. .. Le-privilège-immun,

.. .. Pathologies,

.. .. Ii)-dmla-&-inflammation,

D. .. Physiopathologie-de-la, 30 2.1.2) Les formes tardives de la DMLA

D. .. Caractéristiques-de-la, 2.3.1) Les facteurs de risque avérés en lien avec l'inflammation

.. .. Traitements,

, 3.1.1) Progéniteurs, monocytes et macrophages

D. .. Dans-la, 42 2.3.1.2.1) Les origines de l'inflammation chronique, Accumulation chronique des macrophages

, Rôles des facteurs de risques génétiques

. .. Patho-mécanismes,

.. .. Iii)-neuro-immunité,

. .. Dégénérescence-de-l'epr, 1.3) Impact des cytokines inflammatoires

, Toxicité neuronale induite par les cytokines inflammatoires

.. .. Müller,

.. .. Les, , p.62

. .. Toxicité-du-glutamate,

-. .. Oxytose,

, La production d'IL-1? induit indirectement la mort neuronale

, 2.2.1) Interactions neuro-gliales rétiniennes

. Interactions and .. .. De-müller,

. Lad, Liste des abréviations Subretinal CD14 + mononuclear phagocytes associate with cone segment loss in the transitional zone Using pan-mononuclear phagocyte (MP) markers, we and others have previously shown that the subretinal space (i) above large Drusen, 2003.

. Sennlaub, which is additionally expressed by other members of the MP family (Gautier et al., 2012) and is therefore not discriminative for infiltrating Mos versus resident MPs (unlike CCR2). We analyzed the presence of subretinal CD14 + MPs and cone segment morphology on central RPE/choroid and retinal flat-mounts from 4 age-matched control donor eyes (Figure 2A-D) and 5 donor eyes with central GA lesions (Figure 2E-H), with particular attention to the TZ. Flat-mount immunohistochemistry facilitates the appreciation of cone outer segments and the detection of the smaller, dispersed MPs that are more difficult to detect on sections. We used CD14 immunohistochemistry to visualize MPs, and (iii) in the TZ of patients with GA, 1984.

, peanut agglutinin (PNA,green), and Hoechst nuclear stain (blue, RPE autofluorescence visible in orange) of RPE/choroid-(A and E) and retinal-flatmounts (B-D and F-H) of a control donor (A-D) and a donor with geographic atrophy (GA, panel E-H). (E) 3D reconstruction at higher magnification of a CD14 + cell on RPE flatmounts in an orthogonal (E, upper inset) and perpendicular (E, lower inset). (F) Representative confocal micrographs of CD14 (F, upper inset) -IBA-1 (F, lower inset) double labeling. (D and H) Oblique and perpendicular (insets) 3D reconstruction views of the outer aspect of the retinal flatmounts. The margin of the atrophic zone (AZ), recognized by the loss of RPE (E) and by the irregular cone distribution and a thinned outer nuclear layer (G) is indicated by the yellow dotted line. (G) PNA/arrestin pattern distant (>1000 mm) from the AZ of a patient with GA (G inset), Figure 2. CD14, peanut agglutinin and cone arrestin staining on central flatmount preparations from control and geographic atrophy patients. Representative micrographs of immunohistochemical detection (confocal Z stack projections) of CD14 (white), cone arrestin (red)

. Eandi, , vol.5, 2016.

. Netea, PNA-staining of retinal explants cultured for 18 hr in the absence of Mos (Figure 4B) but with recombinant IL-1b (Figure 4C), showed that IL-1b was sufficient to severely reduce PNA + CS. Quantification of PNA + CS confirmed the significant, IL-1b-induced volume loss (Figure 4D). In these experiments IL-1b was used at a concentration of 50 ng/ml (in the range of concentration classically used in vitro) but the local IL-1b concentration that cones are exposed to in the co-culture is difficult to estimate, as a gradient of IL-1b is expected to form around the IL-1b producing Mos. To directly evaluate the effect of locally produced IL-1b we studied the effect of the IL-1 receptor antagonist (IL-1Ra) on the co-cultures. PNA-stained flatmounts of Mo/retinal co-cultures without (Figure 4E) or in the presence of IL-1Ra (Figure 4F) shows that IL-1b-inhibition significantly protects against Mo-induced CS loss (Figure 4G), Similarly, human blood monocytes constitutively release endogenous ATP, which leads to mature IL-1b after transcriptional induction without a second exogenous stimulus, 2009.

, hMo cultured alone or with a retinal explant for 18 hr (both on polycarbonate filters, n = 5, ANOVA, Dunnett's post test*p=0,0079). (B and C) Oblique and perpendicular (insets) 3D reconstruction views of 18 hr peanut agglutinin (PNA)-stained retinal explant (B) and IL1b (50 ng/ml) exposed explant (C). (D) Quantification of cone segment volume in retinal explants cultured with or without IL-1b (n = 6/group, Mann Whitney *p=0,0087). (E and F) Oblique and perpendicular (insets) 3D reconstruction views of 18 hr peanut agglutinin (PNA)-stained retinal explant cocultured with human monocytes without (E) or with IL-1 receptor antagonist (F, 10 mg/ml). (G) Quantification of cone segment volume in Mo/retinal cocultures with or without an IL-1 receptor antagonist (n = 6/group, Kruskal-Wallis, Dunn's post test *p=0,0022 versus 'without hMo'; ?p=0,0182 versus "with hMo without IL1-Ra). RetEx: retinal explant, The influence of IL-1b retinal explants co-cultures. (A) Quantitative RT-PCR of RT-PCR of IL-1b and IL-18 normalized with S26 mRNA in fresh human monocytes (hMo)

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. Sennlaub, , 2013.

. Bird, In the current study, we used immunohistochemistry on flat-mount preparations with an antibody recognizing a coreceptor of the toll like receptor 2 and 4, CD14, to visualize the infiltration of CD14 + MPs (blood-or tissue-derived MPs) beyond the AZ in the TZ. Co-staining for PNA and cone arrestin confirmed the presence of residual cones in the AZ and the severe CS degeneration in the TZ of retinal flat-mounts and illustrates the close physical association of CS degeneration with CD14 + MPs, GFP/GFP mice (Figure 5D). Strikingly, IL-1b inhibition, which had no effect on subretinal MP accumulation (Figure 5E), completely prevented the loss of PNA + CS volume in the light-challenged mice (Figure 5D), p.10, 2001.

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