Abstract: Objective To explore the mechanism by which long non-coding RNA (lncRNA) Neat1 causes the degeneration of oxygen-induced retinopathy (OIR) in photoreceptor cells, in order to provide new ideas for the prevention and treatment of retinopathy of prematurity (ROP).Methods A mose model of oxygen-induced retinopathy (OIR) was established under the hyperoxia environment. Meanwhile, normal mice at the same age were used as a control group. Though the next-generation sequencing (NGS), the differential lncRNAs related to the abnormal development of the retina in OIR mice were screened out. The differentially expressed genes detected by the chip and the coding genes that were predicted to be the targets of differential lncRNAs were intersected for GO analysis and pathway analysis. Then, qPCR method was used to validate the differentially expressed target genes. LncRNA nuclear paraspeckle assembly transcript 1 (Neat1) was analyzed by the UCSC genome browsing tool. The levels of Neat1 and retinal degeneration protein 3 (RD3) in the retina of OIR mice, and in the blood of ROP children were detected with qPCR. The content of cyclic GMP(cGMP) in the blood of ROP children and the retina of OIR mice were measured by radioimmunoassay.Results According to NGS results, Neat1 was differentially expressed in the retina of OIR mice, which was consistent with the results of qPCR validation. Bioinformatic results predicted that RD3 might be a regulatory target of Neat1, and RD3 gene was found at the downstream of mouse Neat1 sequence. Compared with those in the control groups, increased Neat1 levels were seen, while cGMP were highly expressed but RD3 was lowly expressed in the blood of ROP children, and the retina of OIR mice.Conclusions lncRNA Neat1 may cause the degeneration of retinal photoreceptor cells through the Neat1/RD3/cGMP pathway under the mediation of RD3.