Objectives: A reduction in the scotopic b-wave has been previously reported in approximately 40% of the study groups’ participants (Ritvo et al, 1988). Our aim was to extend this finding by using an extended luminance series and to investigate if any SNPs associated with ASD may help explain any differences seen in the ERG waveforms.
Methods: Participants (N=10 comparison and N=6 ASD) were selected from a panel of volunteers that were matched for verbal, performance and full IQ. ASD participants met DSM-IV criteria confirmed by ADOS and review of clinical notes. Ethical approval was granted by University Ethics committee. ERGs were recorded monocularly using a mini Ganzfeld. Participants were dilated and dark adapted for 20 minutes. Scotopic and photopic luminance functions were recorded between (-2.35 and 1.5 log cd.sec.m). A Naka-Rushton function was fitted to the scotopic limb of the luminance function and the parameters , K and R calculated by linear regression analysis using log[(R/R)-1] = -log L + n log K. In this case, R was set at 1% greater than the maximal b-wave response (R) for a given luminance (L). The parameter n represents retinal homogeneity, R as retinal responsiveness and K as a measure of retinal sensitivity. Additionally, 30 Hz photopic flicker, scotopic oscillatory potentials were recorded.
Genotyping was performed by KBioscience (http://www.kbioscience.co.uk). SNPs were genotyped using the KASPar chemistry- a competitive allele specific PCR SNP genotyping system using FRET quencher cassette oligos (http://www.kbioscience.co.uk/genotyping/genotyping-chemistry.htm). SNPs for the glutamate receptor (GRIK2, rs2235076); GABA A receptor subunits (β1, rs2351299, α4 rs2280073, rs1912960); Aspartate/Glutamate exchanger(SLC25A12, rs2292813); Neural cell adhesion molecule (NRCAM rs2300045); Disrupted in Schizophrenia 1 (DISC, rs1322784) and Neuroligin 4 X-linked (NLGN4X, rs12836764). Currently N=12 ASD and N=10 genotypes are available for (rs2292813, rs2235076, rs2280073, rs2300045 and rs1322784). Further will be performed on the final group of participants which we anticipate a size of 20 in each group.
Results: The ASD group 3/6 participants displayed a reduced luminance response function which is consistent with previous reports. Student’s t-test for the parameters Rmax representing retinal responsiveness (p=0.03), K representing retinal sensitivity (p<0.001) and n retinal homogeneity (p=0.01) were all significantly reduced. No difference was observed in the 30Hz (p=0.51) or oscillatory potentials (p=0.95). Preliminary analysis of SNP data using Chi-squared shows no difference in either allele or genotype frequency between the groups. <
Conclusions: We present preliminary findings that the scotopic retinal sensitivity and responses are altered in ~ 50% of adults with ASD. Genotyping of the individuals may offer insights into the contribution of SNPs associated with ASD in explaining the changes in the retinal luminance response function.