Methods

Male (M) and female (F) C57BL/6JRj mice were divided into 2 treatment groups: Triamcinolone group (5M, 5F) and PBS control group (4M, 4F). To induce GA, laser lesions (9 shots/eye) were induced unilaterally on the temporal side of the optic nerve head in the right eye using an 810 nm infrared laser. Triamcinolone (40 µg/eye, 1 µl) or PBS were administered subconjunctivally at Day -1, Day 13 and Day 28 after the induction. The retinal pathology was assessed using spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) imaging weekly until Day 56. On day 56, animals were sacrificed, and RPE/choroid flat mounts were prepared and immunolabelled with phalloidin and RPE65 antibody to assess the morphology.

Results

In the Triamcinolone group, all females were euthanized due to weight loss prior to Day 28. FAF revealed discrete laser shots at all timepoints in Triamcinolone group, as opposed to merged shots in the PBS control group. SD-OCT imaging showed retinal thickness preservation in Triamcinolone group as compared to PBS control at Day 7 and Day 13 (P<0.001), Day 21 (P=0.008), Day 28 (P=0.02), and Day 56 (P=0.01). However, by Day 56 there was a retinal thickness decrease in Triamcinolone group by 39.8% and in PBS group by 44.2% as compared to baseline. The lesion area was larger in the Triamcinolone group as compared to PBS on Day 35 and Day 49 (P=0.03), and Day 56 (P=0.01). Histopathological assessment did not reveal major differences between the treatment groups in RPE65 and F-actin (phalloidin) stainings.

Conclusions

Subconjunctival administration of triamcinolone delays retinal atrophy in the laser-induced mouse model of GA. However, triamcinolone administration also caused severe adverse effects in female mice. Further testing with triamcinolone is needed to identify the best treatment paradigm for optimal outcome both in male and female mice.

Xavier Ekolle

ARVO 2025

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Authors

Ekolle Xavier, Lappeteläinen Birgitta*, Thapa Rubina, Kolehmainen Anni, Tenhunen Anni, Tähtivaara Leena, Nádai Hajnalka, Vergun Olga, Anne Mari Haapaniemi, Koponen Anna Mari, Partanen Päivi, Lappalainen Eerik, Varis Sanni, Bijeikis Simas, Vähätupa Maria, Giedrius Kalesnykas
*The authors contributed equally