a Distribution of EGFP expression in the scleral whole-mount 28 days after sub-tenon’s capsule injection of adeno-associated virus serotype DJ (AAV-DJ)-EGFP or AAV-DJ-SaCas9 (as non-fluorescence control); scale bar, 1 mm. b Representative Optical Coherence Tomography images 28 days after of each AAV injection; scale bar, 100 µm. c Expression level of IRE1, PERK, and ATF6 protein 28 days after of AAV-SaCas9 with AAV-gRNA against Eif2ak3 (Gene symbol of PERK, gEig2ak3) and/or Atf6 (gAtf6) injections. d Scleral Eif2ak3 and Atf6 knockdown by AAV-DJ-CRISPR/Cas9 injection into sub-tenon’ capsule. After 28 days injection, gene expression in the sclera determined by qPCR (n = 9, respectively). SaCas9 + gScramble group was assigned a value of 1.0. The p values were determined by one-way ANOVA with Tukey HSD. e Effects of scleral Eif2ak3 and/or Atf6 knockdown on axial elongation (sham: n = 5, gScramble: n = 11, gEif2ak3: n = 9, gAtf6: n = 8, gEif2ak3 + gAtf6: n = 8). The p values were determined by two-tailed Generalized Estimating Equations for five groups comparison (sham vs gScramble vs gEif2ak3 vs gAtf6 vs gEif2ak3 + gAtf6) and Student’s two-tailed t-test for two groups comparison (NL vs −30D). NL: No Lens control, −30D: minus 30 D lens-wearing eye. f Effects of scleral Eif2ak3 and/or Atf6 knockdown on refraction (sham: n = 5, gScramble: n = 9, gEif2ak3: n = 9, gAtf6: n = 8, gEif2ak3 + gAtf6: n = 9). The p values were determined by two-tailed Generalized Estimating Equations for five groups comparison and Student’s two-tailed t-test for two groups comparison. g Effects of scleral Eif2ak3 and/or Atf6 knockdown on VCD + RT (sham: n = 5, gScramble: n = 7, gEif2ak3: n = 7, gAtf6: n = 7, gEif2ak3 + gAtf6: n = 7). The p values were determined by two-tailed Generalized Estimating Equations for five groups comparison and Student’s two-tailed t-test for two groups comparison. Source data are provided as a Source Data file.