Figure 7.

Alleviation of Uveitis by Inhibition of Transcriptional Elongation

(A and B) Representative histopathology from an IRBP-immunized mouse treated with vehicle control (n = 6) showing severe EAU (grade 4) (choroid: C; iris: I; lens: L; vitreous: V, A; retinal layer: R; photoreceptors: PR; and retinal pigment epithelium: RPE, B) (yellow lines, retinal layers; red arrows, infiltrating cells; and white arrows, retina folding). Image in (A) is composed of two fields of view.

(C) Representative in vivo fundoscopy of an IRBP-immunized mouse treated with vehicle control, exhibiting large confluent lesions with retinal atrophy.

(D and E) As in (A) and (B), except for mice treated with JQ1 (30 mg/kg) for 5 days. (D) is composed of two fields of view.

(F) As in (C), except for mice treated with JQ1 (30 mg/kg) for 5 days. Only very small, peripheral focal lesions were present.

(G and H) As in (A) and (B), except for mice treated with Flavopiridol (15 mg/kg) for 5 days. (G) is composed of two fields of view.

(I) As in (C), except for mice treated with Flavopiridol (15 mg/kg) for 5 days.

(J) Mean (± SEM) fundoscopy scores for control mice and mice immunized with IRBP with and without treatment with JQ1 and Flavopiridol (left). The EAU retinal histology scores are shown (right) (^∗p < 0.05, ^∗∗p < 0.01, and ^∗∗∗p < 0.005) (unpaired t test with Welch’s correction, two-tailed).

(K) Percentage of IFNγ+, TNFα+, and FasL+ CD4+CD3+ T cells from the retina of non-immunized and IRBP-immunized mice treated with carrier, JQ1, or Flavopiridol (mean ± SD) (^∗p < 0.05 and not significant: ns) (one-tailed Student’s t test).

(L) As in (K), except for Il18r1+ and Ctla4+ CD4+CD3+ populations from the inguinal lymph nodes.

See also Figure S7.