Effects of intravitreal ranibizumab on the untreated eye and systemic gene expression profile in age-related macular degeneration

Figures & data

Figure 1 The differences in central retinal thickness (CRT) over time in treated and untreated contralateral eyes.

Note: Data presented as mean with 95% CI, P<0.05, ANOVA for repeated measures.
Abbreviations: CI, confidence interval; ANOVA, analysis of variance.

Figure 2 The central retinal thickness (CRT) measured by optical coherence tomography before the first dose of treatment and 3 months after the initiation of treatment in treated and untreated contralateral eyes.

Notes: (A) Treated and (B) untreated contralateral eyes. Box and whisker plots present mean ± SE and SD of central retinal thickness; *P<0.05, paired t-test.
Abbreviations: SE, standard error; SD, standard deviation.

Table 1 Changes in gene expression in PBMCs of AMD patients before and after ranibizumab treatment

Fold change	Number of transcripts	P<0.05	P<0.02	P<0.01	P<0.005	P<0.001
FC all	22,283	4,506	2,086	817	25	4
FC >1.1	18,550	4,506	2,086	817	25	4
FC >1.5	9,518	4,474	2,086	817	25	4
FC >2.0	4,799	3,097	1,830	811	25	4
FC >.3.0	1,608	1,078	743	423	25	4

Notes: Volcano plot demonstrates P-value and fold change for transcripts which exhibit differential expression in PBMCs of AMD patients before and after ranibizumab treatment. Black indicates differentially expressed genes with P<0.05 and FC>2.0; gray indicates all genes with P>0.05.

Abbreviations: PBMCs, peripheral blood mononuclear cells; AMD, age-related macular degeneration; FC, fold change.

Table 2 PANTHER classification of biological processes, molecular functions, and cellular components significantly enriched in the set of differentially expressed genes

Biological process	Number of genes (observed/expected)	P-value	Biological process	Number of genes (observed/expected)	P-value
Metabolic process	1,172/925	<0.0001	Biological regulation	431/349	0.0005
Cellular process	865/639	<0.0001	Ion transport	115/74	0.0008
Primary metabolic process	986/771	<0.0001	Cellular component organization	164/114	0.0009
Developmental process	460/306	<0.0001	RNA splicing	56/29	0.0012
Cell communication	486/346	<0.0001	RNA splicing, via transesterification reactions	56/29	0.0012
System development	281/177	<0.0001	Vesicle-mediated transport	144/100	0.0024
Protein metabolic process	426/302	<0.0001	Synaptic transmission	75/45	0.0034
Multicellular organismal process	294/193	<0.0001	Endocytosis	72/43	0.0045
Single-multicellular organism process	294/193	<0.0001	Cellular protein modification process	177/129	0.0050
System process	251/159	<0.0001	mRNA splicing, via spliceosome	67/40	0.0076
Localization	397/283	<0.0001	Nucleobase-containing compound metabolic process	452/379	0.0080
Transport	387/275	<0.0001	Angiogenesis	49/26	0.0102
Neurological system process	203/130	<0.0001	Cellular defense response	69/42	0.0109
Nervous system development	169/108	<0.0001	Cell death	110/75	0.0135
Translation	85/44	<0.0001	Apoptotic process	110/75	0.0135
Mesoderm development	162/103	<0.0001	Death	110/75	0.0150
Intracellular protein transport	208/142	<0.0001	Reproduction	99/66	0.0162
Ectoderm development	153/98	<0.0001	Negative regulation of apoptotic process	39/20	0.0207
Cell–cell signaling	143/90	<0.0001	Heart development	47/26	0.0211
Protein transport	208/144	<0.0001	Visual perception	56/33	0.0218
Response to stimulus	248/179	<0.0001	Muscle organ development	68/42	0.0232
Cation transport	107/64	<0.0001	Cell cycle	196/150	0.0257
Cellular component morphogenesis	113/69	0.0001	Neuron-neuron synaptic transmission	23/10	0.0375
Anatomical structure morphogenesis	119/74	0.0001	Regulation of biological process	287/234	0.0415
Cellular component organization or biogenesis	177/122	0.0002	Gamete generation	86/57	0.0435
Immune system process	250/186	0.0004
Molecular function			Molecular function
Binding	810/637	<0.0001	Cation transmembrane transporter activity	71/40	0.0006
Catalytic activity	759/594	<0.0001	RNA binding	106/69	0.0021
Structural molecule activity	218/135	<0.0001	Nucleic acid binding	429/356	0.0039
Structural constituent of ribosome	60/22	<0.0001	Hydrogen ion transmembrane transporter activity	15/5	0.0255
Protein binding	413/307	<0.0001	Ion channel activity	62/38	0.0316
Transmembrane transporter activity	185/116	<0.0001	Oxidoreductase activity	99/68	0.0344
Transporter activity	192/123	<0.0001	mRNA binding	56/34	0.0378
Receptor binding	163/109	<0.0001	Structural constituent of Cytoskeleton	126/91	0.0436
Receptor activity	230/169	0.0004
Cellular component			Cellular component
Intracellular	213/154	<0.0001	Macromolecular complex	101/70	0.0085
Cell part	230/171	0.0002	Actin cytoskeleton	64/42	0.0311
Ribonucleoprotein complex	31/14	0.0040

Abbreviation: PANTHER, Protein Analysis Through Evolutionary Relationships.

Figure 3 PANTHER classification of differentially expressed genes.

Notes: Based on biological processes (A), molecular functions (B), and cellular components (C).
Abbreviations: PANTHER, Protein Analysis Through Evolutionary Relationships; GO, gene ontology.